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Effector Memory (effector + memory)
Terms modified by Effector Memory Selected AbstractsHomeostatic regulation of T effector to Treg ratios in an area of seasonal malaria transmissionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2009Olivia C. Finney Abstract An important aspect of clinical immunity to malaria is the ability to down-regulate inflammatory responses, once parasitaemia is under control, in order to avoid immune-mediated pathology. The role of classical (CD4+CD25+CD127lo/,FOXP3+) Treg in this process, however, remains controversial. Thus, we have characterized the frequency, phenotype and function of Treg populations, over time, in healthy individuals in The Gambia. We observed that both the percentage and the absolute number of CD4+FOXP3+CD127lo/, T cells were higher among individuals living in a rural village with highly seasonal malaria transmission than among individuals living in an urban area where malaria rarely occurs. These CD4+FOXP3+CD127lo/, T cells exhibited an effector memory and apoptosis-prone phenotype and suppressed cytokine production in response to malaria antigen. Cells from individuals exposed to malaria expressed significantly higher levels of mRNA for forkhead box P3 and T-box 21 (T-BET) at the end of the malaria transmission season than at the end of the non-transmission season. Importantly, the ratio of T-BET to forkhead box P3 was remarkably consistent between populations and over time, indicating that in healthy individuals, a transient increase in Th1 responses during the malaria transmission season is balanced by a commensurate Treg response, ensuring that immune homeostasis is maintained. [source] Impact of human immunodeficiency virus 1 infection and inflammation on the composition and yield of cervical mononuclear cells in the female genital tractIMMUNOLOGY, Issue 1pt2 2009Nonhlanhla N. Nkwanyana Summary Cervical cytobrush sampling is a relatively non-invasive method for obtaining mucosal cells from the female genital tract. To define mucosal immune cells sampled by cervical cytobrushing and to validate this approach for local immunity studies, we investigated the impact of human immunodeficiency virus (HIV) status and inflammation on the yield and composition of cervical cytobrush specimens. Cervical cytobrush samples were obtained from 89 chronically HIV-infected and 46 HIV-negative women. The HIV-infected women had significantly higher yields of CD3+, CD45+, CD19+, CD14+, Langerin+ and CD24+ cells than the uninfected women. While cytobrush-derived T cells from uninfected women were predominantly CD4+ (4·2 CD4 : 1 CD8), CD8+ T cells were predominant in HIV-infected women (0·6 CD4 : 1 CD8). The majority of CD4+ and CD8+ T cells from HIV-infected and uninfected women were of the effector memory (CD45RA, CCR7, CD27,) phenotype. HIV-infected women had significantly elevated levels of interleukin (IL)-1,, IL-6 and IL-8 in cervical supernatants compared with uninfected women. We observed a significant positive correlation between T-cell counts and IL-1,, tumour necrosis factor (TNF)-, and IL-12 concentrations. Neutrophil counts correlated significantly with cervical concentrations of IL-1,, TNF-,, IL-8, IL-6 and IL-10. Antigen-presenting cell numbers correlated significantly with TNF-, and IL-12 concentrations. HIV-infected women on antiretroviral therapy had similar levels of cervical lymphocyte infiltration and inflammation to women naïve to therapy. In conclusion, we suggest that inflammation at the cervix and HIV infection are likely to be key determinants in the absolute number of mucosal immune cells recovered by cervical cytobrushing. [source] Characterization of CC-chemokine receptor 7 expression on murine T cells in lymphoid tissuesIMMUNOLOGY, Issue 2 2003Olle Bjorkdahl Summary Expression of the lymph node homing and CC-chemokine receptor 7 (CCR7), with L-selectin (CD62L), has been shown to divide human memory T cells into two functionally distinct subsets. We generated a polyclonal antibody against murine CCR7 and used this antibody to study CCR7 expression on murine T-cell subsets. Using flow cytometric staining of T cells for visualisation expression of CCR7 in association with CD62L and CD44, a major population of CD4 or CD8 T cells expressing CCR7 were found to be CD62Lhigh CD44low, which would suggest a naïve cell phenotype. By analogy with human studies, memory cells could be subdivided into CCR7high CD62Lhigh CD44high (central memory) and CCR7low CD62Llow CD44high (effector memory). The proportions of these populations were different in lymph node, blood and spleen. Functional, short-term in vitro polyclonal stimulation of blood, spleen and lymph node cells from naive mice demonstrated that CCR7high CD4 T cells produced predominantly interleukin (IL)-2, whereas CCR7low CD4 T cells produced both IL-2 and interferon-, (IFN-,). However, in contrast to previously published reports, the CCR7high CD8 T-cell subpopulation produced both IFN-, and IL-2. Analysis of effector T cells, induced by immunization in vivo, showed that a proportion of activated naïve CD4 T cells down-regulated CCR7 only after multiple cell divisions, and this coincided with the down-regulation of CD62L and production of IL-4 and IFN-,. Finally, analysis of effector T cells during the phase of maximal clonal expansion of secondary immune responses in vivo indicated that the vast majority of both IL-2- and IFN-,-producing cells are CCR7low, while few cytokine-expressing CCR7high T cells were detected. Our results support the hypothesis, developed from studies with human cells, that CCR7 may separate functionally different murine memory T-cell subpopulations, but indicate additional complexity in that CCR7high CD8 T cells also may produce IFN-,. [source] Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humansLIVER TRANSPLANTATION, Issue 9 2007Hiroto Egawa We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8+ alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8+CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27,CD28, subsets, interferon-gamma (IFN-,), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12R,1+ cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance. Liver Transpl 13:1262,1271, 2007, © 2007 AASLD. [source] An early commitment to expression of a particular TCRV, chain on CD8+ T cells responding to attenuated Plasmodium berghei sporozoites is maintained following challenge with infectious sporozoitesPARASITE IMMUNOLOGY, Issue 9-10 2010J. M. LUMSDEN Summary Protection induced by irradiated Plasmodium berghei sporozoites (Pb,-spz) in mice is linked to CD8+ T cells specific for exo-erythrocytic-stage Ags, and intrahepatic memory CD8+ T cells are associated with protracted protection. However, the Ag specificity of the protective CD8+ T cells remains largely unknown. In this study, we characterized the TCR V, usage by intrahepatic CD8+ T cells during ,-spz immunization and after the challenge with infectious Pb sporozoites. The repertoire of naïve (TN) and central memory (TCM) CD8+ T cells was diverse and conserved between individual mice, and did not change with immunization. In contrast, preferential usage of one or more TCR V, subset was observed in effector memory (TEM) CD8+ T cells after immunization. The expanded TCR V, varied between individual mice but V,4, 6, 7, 8.3, 9 and 11 were the most frequently expressed. In addition, there was a correlation in the TCR V, usage by ,-spz-induced CD8+ TEM in the liver and blood of individual mice. The expansion pattern of blood CD8+ TEM did not change with challenge and remained the same for 8 weeks thereafter. These results demonstrate that immunization with ,-spz skews the TCR V, repertoire of CD8+ TEM, and commitment to a particular TCR V, expression is maintained long-term. [source] Immune Reconstitution Following Rabbit Antithymocyte GlobulinAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010S. Gurkan Depletional induction therapies are routinely used to prevent acute rejection and improve transplant outcome. The effects of depleting agents on T-cell subsets and subsequent T-cell reconstitution are incompletely defined. We used flow cytometry to examine the effects of rabbit antithymocyte globulin (rATG) on the peripheral T-cell repertoire of pediatric and adult renal transplant recipients. We found that while rATG effectively depleted CD45RA+CD27+ naïve and CD45RO+CD27+ central memory CD4+ T cells, it had little effect on CD45RO+CD27, CD4+ effector memory or CD45RA+CD31,, CD45RO+CD27+ and CD45RO+CD27, CD8+ T cell subsets. When we performed a kinetic analysis of CD31+ recent thymic emigrants and CD45RA+/RO+ T cells, we found evidence for both thymopoiesis and homeostatic proliferation contributing to immune reconstitution. We additionally examined the impact of rATG on peripheral CD4+Foxp3+ T cells. We found that in adults, administration of rATG-induced peripheral expansion and new thymic emigration of T cells with a Treg phenotype, while CD4+Foxp3+ T cells of thymic origin predominated in children, providing the first evidence that rATG induces Treg in vivo. Collectively our data indicate that rATG alters the balance of regulatory to memory effector T cells posttransplant, providing an explanation for how it positively impacts transplant outcome. [source] Urinary CD4+ effector memory T cells reflect renal disease activity in antineutrophil cytoplasmic antibody,associated vasculitisARTHRITIS & RHEUMATISM, Issue 9 2009Wayel H. Abdulahad Objective Numbers of circulating CD4+ effector memory T cells are proportionally increased in patients with proteinase 3 antineutrophil cytoplasmic antibody,associated vasculitis (AAV) whose disease is in remission and are decreased during active disease, which presumably reflects their migration toward sites of inflammation. Since renal infiltrating cells may appear in urine, we investigated the presence of CD4+ effector memory T cells in urinary sediment as a reflection of renal disease activity in AAV. Methods CD4+ effector memory (CD45RO+CCR7,CD3+CD4+) T cells were quantitated in the urine and peripheral blood of patients with AAV with renal involvement (n = 33), patients with AAV without renal involvement (n = 18), patients with AAV whose disease was in remission (n = 29), and patients with active disease (n = 22), using 4-color flow cytometric analysis. Numbers and percentages of urine CD4+ effector memory T cells in 12 patients with AAV with active renal disease were obtained over several weeks of followup during remission induction. Results A notable increase in urine CD4+ effector memory T cell numbers was observed in patients with active renal AAV compared with patients whose disease was in remission and patients with active disease without renal involvement. The increase in these cells in the urine of patients with active renal AAV was accompanied by a reciprocal decrease in these cells in peripheral blood. Results from followup analysis showed a clear reduction in urine CD4+ effector memory T cells following treatment. Moreover, a negative correlation was observed between percentages of circulating and urine CD4+ effector memory T cells, consistent with their migration toward sites of inflammation. Conclusion Our findings indicate that the presence of CD4+ effector memory T cells in urine reflects renal involvement in AAV. Flow cytometric analysis of these cells in urine may contribute to assessing renal disease activity in patients with AAV. [source] |