These cells have a far greater capacity for cytokine biosynthesis [37] as well as a longer half-life in blood (approximately 3 days) [39] than neutrophils (approximately 6.5 h) [40]. In addition, other abundant cytokines such as G-CSF, MCP-1, IL-6 and IFNγ are absent in neutrophils and were probably mainly derived from monocytes. On the other hand, IL-17 [35], IFN-γ and IL-2 [41] were exclusively derived from lymphocytes, Th17 and Th1 cells, respectively. One explanation ICG-001 clinical trial for the AndoSan™-promoted reduction in LPS-induced inflammatory response in blood ex vivo as well as in patients with IBD may be the following: AndoSan™ may

actually inhibit LPS-induced TLR4 signalling because (1) AndoSan™ stimulates TLR2 [12], which has a common intracellular downstream pathway with the LPS receptor TLR4

for the activation of transcription factor NF-κB, and (2) the inflammation in patients with IBD may in fact partly be because of gram-negative bacterial (LPS)-induced inflammatory response. The second major finding in this study was that the patients with UC had a significant reduction PD0325901 mouse in faecal calprotectin on day 12, whilst calprotectin in plasma was unaltered during the experiment. Calprotectin, an abundant cytosolic protein in neutrophils [26] can, when released to faeces, be used as a marker for disease activity in IBD [27, 29]. Also in patients with CD, reduction in faecal calprotectin has been detected in parallel with reduced degree of inflammation, but then the reported initial calprotectin values were much higher (approximately 15-fold) [27] than here and probably from more seriously affected patients than in the current study. Together with the limited time-span of AndoSan™ ingestion, this difference Chloroambucil may contribute to explain the lack of effect on faecal calprotectin levels in our patients with CD. Interestingly, there was no reduction in plasma calprotectin by mushroom consumption, which indicates that the effect of AndoSan™ on that parameter was local in the colonic mucosa. During

active inflammation, neutrophils infiltrate the lamina propria, crypt epithelium and form crypt abscesses. These histological changes return to normal levels in periods of remission [34]. Although not systematically registered, patients with both UC and CD spontaneously reported a reduction in stool frequency after a few days of AndoSan™ intake, which at least partly may be ascribed to the reduction in faecal calprotectin. Similar to experiments with healthy volunteers consuming the AbM-based mushroom extract [18], there were no pathological effects whatsoever on haematological parameters, including CRP values and leucocyte counts, and negative clinical side effects were not registered. The AndoSan™ mushroom extract mainly containing A. blazei Murill (AbM) (∼83%) but also H.

Drs Miller, Chan, Wiik and Misbah have no disclosures. Dr Luqmani has received consultancy fees from Roche and honoraria from Schering Plough and Wyeth. “
“Surface expression of the IL-2 receptor α-chain (CD25) has been used to discriminate between CD4+CD25HIFOXP3+ regulatory T (Treg) cells and CD4+CD25NEGFOXP3− non-Treg cells. However, this study reports that the majority of resting human memory CD4+FOXP3− T cells expresses intermediate levels of CD25 and that CD25 expression can be used to delineate a functionally distinct memory subpopulation. The CHIR-99021 purchase CD25NEG memory T-cell population contains the vast majority of late differentiated cells that respond to antigens

associated with chronic immune responses and are increased in patients with systemic

lupus erythematosus (SLE). In contrast, the CD25INT memory T cells respond to antigens associated with recall responses, produce a greater array of cytokines, and are less dependent selleck chemicals llc on costimulation for effector responses due to their expression of CD25. Lastly, compared to the CD25NEG and Treg-cell populations, the CD25INT memory population is lost to a greater degree from the blood of cancer patients treated with IL-2. Collectively, these results show that in humans, a large proportion of CD4+ memory T cells express intermediate levels of CD25, and this CD25INTFOXP3− subset is a functionally distinct memory population that is uniquely affected by IL-2. T-cell survival and effector function are sensitive to the availability of essential cytokines

during development, homeostasis, and activation. Interleukin-2 (IL-2) is a 15.5 kDa α-helical protein discovered for its ability to culture T cells long term in vitro [1]. IL-2 has broad effects on T lymphocytes, including survival, proliferation, activation-induced cell death (AICD), T-cell differentiation, cytokine production, and immune tolerance [2-4]. The high-affinity receptor for IL-2 (IL-2R) is composed of three subunits, the α-subunit (CD25), β-subunit (CD122), and the common Aprepitant γ-chain (CD132). CD122 and CD132 are also subunits for other cytokine receptors, whereas CD25 is specific to the IL-2 receptor. IL-2 signaling occurs exclusively through the cytoplasmic tails of CD122 and CD132; CD25 has a short cytoplasmic tail and is not involved in IL-2 signaling. Instead, CD25 has the highest affinity for IL-2 among the individual subunits and acts as an affinity converter [2]. At high concentrations, IL-2 can signal in the absence of CD25 through CD122 and CD132, which form the intermediate-affinity IL-2R. However, CD25 in addition to CD122 and CD132 is required to respond to low concentrations of IL-2 by forming the high-affinity IL-2 receptor [2]. Once formed, the IL-2/CD25/CD122/CD132 quaternary complex is short-lived (t1/2 10–20 min) on the cell surface [5]. Upon internalization, IL-2, CD122, and CD132 are targeted for lysosomal degradation, whereas CD25 is recycled to the cell surface [6, 7].

Through the years, researchers and people in general have tried to demonstrate beyond doubt that mercury in amalgam fillings will cause severe general disease symptoms as well as contact allergy reactions in the oral mucosa. Increased IFN-γ levels were indeed demonstrated in mercury-stimulated lymphocyte cultures from patients suspected of amalgam-induced mucosal affection compared to healthy individuals [30]. This could be indicative of a CS reaction. No difference was, however, found in lymphocyte proliferation or IL-2R expression [30], indicating that a T-cell proliferative reaction like in an allergic reaction

was not at hand. Transient exposures of dentifrice to engineered human oral mucosa resulted in increased IL-1β, whereas IL-8 and TNF-α were down-regulated [31] not supporting a developing CS reaction. The oral

mucosa can be used https://www.selleckchem.com/products/XAV-939.html as a site for developing tolerance. Y-27632 Instead of the classical subcutaneous immunotherapy, a capsule containing allergens is put under the tongue for treating asthmatic IgE-driven inflammatory reactions [2, 32–34]. This treatment modality is potentially skewing the immune system towards a Th1 reaction with IFN-γ production instead of a Th2 reaction with IL-4 and IL-13 production [35] and may as a detrimental side effect lead to inflammatory DTH reactions within the oesophagus [36]. Favouring the Th1-driven inflammatory reactions locally in the oral mucosa would result in local T-cell-mediated and dominated inflammatory reactions such as oral mucosa lichenoid reactions. The characteristics of the oral mucosa to respond to haptens with CS reactions similar to skin reactions are here demonstrated by the local production of cytokines IL-2 and IFN-γ at the site of hapten exposure and in the regional lymph nodes. Furthermore, the regional

lymph nodes weight gains corresponded to the increases in total cell counts and thus underline the development and presence of an allergic hypersensitivity reaction. The oral mucosa is exposed to a vast number of foreign materials constantly (dental restorative materials) as well as transient substances (nutrition and dental care items). The number of substances in contact with oral mucosal membranes constantly TCL poses a challenge to the immune system that needs to be reactive but also to be able to induce tolerance. The common ectodermal origin and the similarity of the CS reactions on skin and in buccal mucosa indicate that these tissues share common immunological patterns of Th1 cell reactivity, at least in dealing with haptens like OXA. “
“The NLRP3 inflammasome plays a critical role in regulating inflammatory and cell death pathways in response to a diverse array of stimuli. Activation of the NLRP3 inflammasome results in activation of the cysteine protease caspase-1 and the subsequent processing and secretion of the proinflammatory cytokines IL-1β and IL-18.

58 The reduction in antiviral capacity in the presence of SP may in part be explained by electrostatic interactions between cationic SP polyamines and the polyanions of the microbicide candidates. This reduction in the inhibitory activity of polyanionic microbicides has also been observed in clinical trials.59,60 Semen from HIV-1-positive individuals contains CF HIV-1 particles and soluble complement components.61 Opsonization with complement was previously shown to enhance HIV-1 infection of T and B cells, monocytes and macrophages.61 Complement receptors are expressed on the apical surface of epithelial cells, DCs, and macrophages.61 Bouhlal et al.61

showed that both R5- and X4-tropic HIV-1 strains can www.selleckchem.com/products/mi-503.html activate complement in seminal fluid in vitro. They found that enhancement of HIV-1 infection in colorectal cell lines (HT-29) was complement dependent. Infection of HT-29 cells with HIV-1 that was pre-opsonized with complement (C3 and C9) in seminal fluid resulted in an enhanced (1.5–2-fold) rate of HIV-1 infection compared to infection of these cells in the presence of virus alone.61 R5- and X4- strains activate complement in seminal fluid and generate Staurosporine C3 cleavage fragments (C3a/C3adesArg).61 The immediate reaction of semen deposition into the mammalian reproductive tract is

a dramatic influx of inflammatory cells.62–64 Changes in the leukocyte population of the female reproductive tract (FRT) after introduction of the male ejaculate have been well documented in mice, pigs, rabbits, and women.63,65–67 Most of these pro-inflammatory effects in animals are attributed to the presence of transforming growth factor (TGF)-β in SP.68,69 The majority of TGF-β present in male SP is synthesized in latent form and appears to be

activated by plasmin and other enzymes in the FRT.69 Women respond to semen deposition with a similar influx of leukocytes, especially to the cervix, called leukocytic reaction. These leukocytes predominantly include neutrophils and to a lesser extent macrophages and T lymphocytes.63,64 SP is also considered a cause of recurrent vaginitis in certain sexually active women, a condition possibly related to SP protein allergy and Urocanase associated with localized irritation and inflammation.70 The etiology of this inflammatory response, however, is not well understood. The semen-induced leukocyte influx to the FRT is believed to be mediated by chemoattracting factors released by the epithelial lining of the FRT in response to sperm and SP.62 Although a transient, semen-induced inflammation of the FRT is probably necessary for a successful establishment of pregnancy, it also recruits and activates HIV target cells to the portals of virus entry, thus facilitating mucosal infection and HIV transmission. SP induces differential expression of inflammatory genes in human cervical and vaginal epithelial cells.71 In ectocervical cells, these genes include IL-8, IL-6, CSF2, CCL2, GM-CSF, and MCP-1.

We have previously

shown that NY-ESO-1–specific CD4+ T cells are detectable in cancer patients with spontaneous NY-ESO-1 serum Ab responses [17, 18]. In addition, NY-ESO-1–specific CD4+ T-cell precursors can expand and become detectable in healthy Selleckchem Pritelivir individuals after in vitro antigenic stimulation of peripheral CD4+ T cells, but only following depletion of CD4+CD25+ T cells [19, 20]. These results suggested that NY-ESO-1–specific CD4+ T-cell precursors are actually present at relatively high frequencies in healthy individuals, and that the activation/expansion of NY-ESO-1–specific naive CD4+ T cells is suppressed by CD4+CD25+ Treg cells. In healthy donors and in cancer patients with NY-ESO-1–expressing tumors but without spontaneous Rapamycin nmr anti-NY-ESO-1 Ab (seronegative), naturally arising NY-ESO-1–specific T-cell responses are susceptible to Treg-cell suppression and are exclusively detected from naive populations (CD4+CD25−CD45RA+). In contrast, most NY-ESO-1–specific CD4+ T cells in cancer patients with spontaneous anti-NY-ESO-1 Ab (seropositive) are derived from memory populations (CD4+CD25−CD45RO+) and are detectable even in the presence of CD4+CD25+ Treg cells [20, 21]. After vaccination with HLA-DPB1*0401/0402-restricted

NY-ESO-1157–170 peptide in incomplete Freund’s adjuvant, ovarian cancer patients develop NY-ESO-1–specific CD4+ T cells with only low avidity to antigen and low sensitivity to Treg cells, even though they

have an effector/memory phenotype (CD4+CD25−CD45RO+) [21]. Still, high-avidity naive NY-ESO-1–specific T-cell precursors are present in the peripheral blood of vaccinated patients, but they are subjected to continuous CD4+CD25+ Treg-cell suppression throughout vaccination [21]. Thus, a strategy to overcome Treg-cell suppression on preexisting high-avidity naive T-cell precursors is an essential component for effective cancer vaccines. Accumulating data shed light on recognition of pathogen-associated molecular patterns through TLRs to break the suppressive environment cAMP in tumors [22]. It has been reported that TLR stimulants, such as lipopolysaccharide or CpG, block the suppressive activity of CD4+CD25+ Treg cells partially by an IL-6–dependent mechanism [23]. TLR2 signaling was reported to stimulate the proliferation of CD4+CD25+ Treg cells and to induce temporal loss of suppressive activity of CD4+CD25+ Treg cells [24]. TLR2 signaling has also been shown to increase IL-2 secretion by effector T cells, thereby rendering them resistant to CD4+CD25+ Treg-cell–mediated suppression [25].

In this region, elongated tumor cells were observed radiating toward a central vessel to form characteristic papillary structures. Immunohistochemically,

three cases showed strong reactivity for GFAP, and one exhibited Alpelisib clinical trial weak reactivity. All cases were focally positive for epithelial membrane antigen, CD34 and D2-40, but negative for neurofilament protein (NFP). Several ultrastructural investigations have supported the ependymal origin of chordoid glioma. In some cases of immunoreactivity for NFP, some authors have supposed that chordoid glioma originates from a multipotential stem cell with glial and neuronal cell differentiation. With regard to the present four cases with immunoreactivity for D2-40 (an ependymal marker) and CD34 (undifferentiated neural precursors) and based on previously published data, we considered that the majority of chordoid gliomas had an ependymal origin, and that a small minority might have originated from a multipotential stem cell having ependymal and neuronal cell differentiation. “
“This chapter contains sections titled: Introduction Anatomy and Function of the Olfactory Mucosa and Olfactory Tract Preparation of the Olfactory Mucosa for Neuropathology Examination Special Procedures for Neuropathology Evaluation of the Olfactory

Mucosa Neuropathology of the Olfactory Mucosa and Olfactory Tract: Basic Principles Comparative Neuropathology www.selleckchem.com/products/AG-014699.html of the Olfactory Mucosa and Olfactory Brain Toxicological Neuropathology of the Vomeronasal Organ References “
“CNS involvement by systemic Hodgkin lymphoma (HL) is quite rare, but the disease limited to the CNS is an exceptionally rare entity. The incidence of CNS-HL has been estimated at 0.2–0.5% of cases, but a more recent study has modified that figure to less than 0.02%. Like the conventional form, the diagnosis of primary CNS-HL rests upon distinct morphological and immunohistochemical characteristics, including diagnostic Reed-Sternberg cells, in addition to staging studies demonstrating a lack of disease elsewhere. The paucity Protirelin of cases

in the literature precludes reliable clinical and demographic data, as well as a consensus on treatment and prognosis. We present two cases of primary cerebellar HL, one with 10-year follow-up, and a relevant review of the literature. “
“Aceruloplasminemia is characterized by progressive neurodegeneration with brain iron accumulation due to the complete lack of ceruloplasmin ferroxidase activity caused by mutations in the ceruloplasmin gene. Redox-active iron accumulation was found to be more prominent in the astrocytes than in the neurons. The most characteristic findings were abnormal or deformed astrocytes and globular structures of astrocytes. The lack of ceruloplasmin may primarily damage astrocytes in the aceruloplasminemic brains as a result of lipid peroxidation due to massive iron deposition.

However, IL-10-deficient mice have more severe bone loss than WT mice in our periapical lesion model,7 suggesting that if OPN is acting Saracatinib price to regulate IL-10 expression then OPN-deficient mice would be protected from bone loss, rather than the increased susceptibility

we observed. Together, these considerations suggest that OPN function in these periapical lesions is independent of its effects on IL-10 expression, and most likely related to its function in regulating the innate immune system. Osteopontin has multiple effects on cells of the myeloid lineage.8 It is chemotactic for neutrophils,33,34 although its effects on these cells are still not well understood. Osteopontin is also chemotactic for macrophages, and enhances migration of this cell type14,35–38 in response to some, but not all, chemoattractants. The see more OPN-deficient macrophages are defective in killing tumour cells39

and bacterial cells,31 and defective phagocytosis has also been reported.40 Our results are consistent with these reports, suggesting that OPN deficiency results in increased neutrophil persistence in vivo in response to bacterial infection. So, increased neutrophil elastase levels in OPN-deficient mice may be a reflection of a defect in neutrophil killing or clearance mediated by macrophages or may reflect an alteration in neutrophil function in the absence of OPN. An alternative explanation, that OPN deficiency results in increased recruitment of neutrophils to the site of infection, is also possible, although this would be unexpected, based on the known effects of OPN on cell migration. Analysis of these lesions at different times of infection is required to understand the detailed mechanism of this effect. Defects in macrophage function or accumulation have been previously shown to result in increased bone loss in these endodontic infections.5 In the absence of the macrophage chemoattractant MCP-1, monocyte recruitment

to the site of infection is impaired, selleckchem and the resulting bone loss is significantly increased. A similar mechanism may be occurring in the absence of OPN. However, neutrophil defects are strongly associated with the tissue damage in both human and experimental endodontic infections (reviewed in ref. 2), so we cannot rule out an effect of OPN on this cell type as well. The effects of OPN on phagocytes are probably mediated through its ability to bind to the integrins important in myeloid cells: the αvβ3, and the α4β1 and α9β1 integrins.41–43 The innate immune response to infection includes a rapid accumulation of neutrophils at the site of infection: these cells make a variety of toxic products that can kill invading bacteria, but also cause tissue damage.

57 by 21 days. Vessel diameters did not change whereas complexity Roxadustat and density did, signaling remodeling. Conclusions:  This new automated analysis identified design parameters for tissue engraftment and could be used in other models of graft vessel biology to track proliferation and pruning of complex vessel beds. “
“Please cite this paper as:

Guo, Itoh, Toriumi, Yamada, Tomita, Hoshino and Suzuki (2011). Capillary Remodeling and Collateral Growth Without Angiogenesis After Unilateral Common Carotid Artery Occlusion in Mice. Microcirculation 18(3), 221–227. Objective:  To clarify the mechanisms of blood flow restoration after major artery occlusion, we presented first dynamic changes in cortical vessel morphology observed through a cranial window in mice after unilateral common carotid artery (CCA) occlusion. Methods:  The density and diameter of capillaries, as well as diameters of pial arteries, were measured by confocal laser-scanning microscopy and fluorescent microscopy, respectively. Possible angiogenesis was evaluated https://www.selleckchem.com/products/hydroxychloroquine-sulfate.html by detecting any outgrowth of endothelial cells from pre-existing vessels or intussusception

in Tie2-GFP mice. Results:  Immediately after unilateral CCA occlusion, cerebral blood flow (CBF) index, the reciprocal of mean transit time, reduced significantly and returned to the previous level after 14 days. Repeated observation of the cortical vessels did not reveal any angiogenesis, whereas the cortical capillary diameter increased by 74% after 14 days. The anterior cerebral artery (ACA) and collateral vessels connecting ACA and middle cerebral artery also dilated significantly. The capillary dilatation to the size of arteriole in the settings of collateral growth and CBF restoration suggested capillary remodeling. Conclusions:  Our results indicate that capillary remodeling, pial artery dilatation and collateral growth without angiogenesis are sufficient mechanisms to restore normal cerebral blood flow

after unilateral CCA occlusion. “
“This chapter contains sections titled: Mouse Embryo Manipulations for Live Imaging Imaging Vascular Development and Microcirculation Using Confocal Microscopy of Vital Fluorescent Markers Live Imaging of Mammalian Embryonic Development and Circulation with OCT Summary References “
“Please Immune system cite this paper as: Doyle and Haas (2010). The Angiogenic Response to Skeletal Muscle Overload is not Dependent on Mast Cell Activation. Microcirculation17(7), 548–556. Objective:  To determine if mast cell activation in skeletal muscle contributes to overload-induced angiogenesis. Methods:  Extensor digitorum longus muscle was overloaded through extirpation of the synergist muscle tibialis anterior. Muscles were removed after 1, 2, 4, 7 or 14 days, and mast cell density and degranulation were quantified by histology. The mast cell stabilizer, cromolyn, was administered acutely or chronically to test if mast cell degranulation contributes to overload-induced angiogenesis.

Finally, the role of the inflammasome in host defense (e.g. influenza) and disease pathogenesis (e.g. cerebral malaria, Alzheimer’s disease, diabetes) remains poorly understood. Work in our laboratory is supported by NIH grants AI063331, AI064748 and AI064748. We thank Jurg Tschopp for sharing manuscript prior to publication. L. F. was a recipient of a postdoctoral fellowship from the Arthritis Foundation. Smad inhibitor T. E. was supported by a Fellowship from the Deutsche Forschungsgemeinschaft (DFG) Germany and T.

R. by a Fellowship from the Swiss National Science Foundation. We apologize to many investigators whose important work was not explicitly cited due to space constrains. Conflict of interest: The authors declare no financial or commercial conflict of interest. See accompanying Viewpoint: http://dx.doi.org/10.1002/eji.200940207 “
“The pathogenesis of nasal polyposis remains unclear; it severely affects patients’ quality of life and complicates inflammation in adjacent organs such as sinusitis and asthma. Aberrant immune regulatory function in these patients is proposed. The present study aims to examine the regulatory T cells (Treg) in nasal mucosa of patients with allergic rhinitis (AR) and nasal polyposis (NP). Patients with AR or AR/NP were

treated with inferior turbinectomy for their inferior turbinate hyperplasia. Surgically removed nasal mucosa was collected to examine the Treg by immunohistochemistry and flow cytometry. The results showed that more forkhead box P3 (FoxP3)+ cells were found in AR with polyps than in those with AR alone. Further studies revealed that these FoxP3+ Protease Inhibitor Library nmr T cells from AR/NP group also expressed interleukin (IL)-17. In vitro study showed that staphylococcal enterotoxin B (SEB) induced CD4+ FoxP3+ T cells to become FoxP3+ IL-17+ cells via facilitating the expression of IL-6, that in synergy with transforming growth factor-beta, induce the expression of IL-17 in FoxP3+ cells. We conclude that FoxP3+ IL-17+ T cells were localized in the nasal mucosa of BTK inhibitor patients with AR and NP. SEB may play a role in converting FoxP3+ Treg to FoxP3+ IL-17+ T cells. The presence of IL-17+ FoxP3+ T cells

may play a role in the remodelling of the nasal airways in certain people who develop polyps, irrespective of whether or not they are atopic. It has been noted that a correlation exists between nasal allergy (AR) and nasal polyposis (NP) [1–3]; however, the underlying mechanism remains to be further understood. Functional deficiency or decrease in the number of regulatory T cells (Treg) plays a critical role in allergic diseases [4]. However, the properties of Treg in upper airway mucosa need to be further elucidated. Forkhead box P3 (FoxP3) is a transcription factor in CD4+ CD25+ Treg that is regarded as a signature molecule in CD4+ Treg[5]. Recent studies indicate that there is a subset of CD4+ FoxP3+ T cells that express interleukin (IL)-17 [6,7].

Cells of lighter density were isolated by centrifugation as described above for analysis by flow cytometry. Bacterial load in spleens of infected mice was also determined by plating out serial diluted homogenates on horse blood agar plates [23]. Two-tailed, unpaired Student’s t-test was used to assess significant differences between groups. Prism (Graphpad Software, La Jolla, CA, USA) was used for click here graphs and statistical analysis. Differences were considered significant when the p-value was less than 0.05. We thank Dannielle Cooper, Catherine Yates, and Melissa Smith for assistance with animal injection and organ extraction. We thank Jamie Brady for careful reading of the manuscript. This work was

supported by National Health and Medical Research Council of Australia (NHMRC) Project grants (#1006428 to YX; #637324 and #1007703 to YZ), Program grant (#516700 to AL), Juvenile Diabetes Research Foundation Project grant (#112613 to AL), NHMRC Independent Research Institutes Infrastructure Support Scheme grant, and Victorian State Government Operational

Infrastructure Support grant. The authors declare no financial or commercial conflicts of interest. Disclaimer: Supplementary Dabrafenib in vivo materials have been peer-reviewed but not copyedited. Figure 1. Signaling of GM-CSF on DC development. Figure 2. (A) Antigen presentation by BM-DCs. Figure 3. Expression of IRF8 by DC subsets. Figure 4. Limiting dilution of DC development from pro-DCs. “
“It has been reported that the initiation of highly

active anti-retroviral therapy (HAART) is associated with why the development of reversal reaction (RR) in co-infected HIV/leprosy patients. Nevertheless, the impact of HIV and HAART on the cellular immune response to Mycobacterium leprae (ML) remains unknown. In the present study, we observed that ex vivo peripheral blood mononuclear cells (PBMCs) of both RR and RR/HIV patients presented increased percentages of activated CD4+ T cells when compared with the healthy individuals (HC) group. The frequency of CD8+ CD38+ cells increased in the PBMCs of RR/HIV patients but not in RR patients when compared with the HC group. Both RR and RR/HIV skin lesion cells presented similar percentages of activated CD4+ cells, but the numbers of activated CD8+ cells were higher in RR/HIV in comparison to the RR group. The frequency of interferon-γ-producing cells was high in response to ML regardless of HIV co-infection. In ML-stimulated cells, there was an increase in central memory CD4+ T-cell frequencies in the RR and RR/HIV groups, but an increase in central memory CD8+ T-cell frequency was only observed in the RR/HIV group. ML increased granzyme B+ effector memory CD8+ T-cell frequencies in the RR/HIV PBMCs, but not in the HC and RR groups. Our data suggest that the increased expression of effector memory CD8+ T cells, together with greater perforin/granzyme B production, could be an additional mechanism leading to the advent of RR in co-infected patients.