Memory Subsets (memory + subset)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Expression of CD8, identifies a distinct subset of effector memory CD4+ T lymphocytes

IMMUNOLOGY, Issue 2 2006
Iole Macchia
Summary Circulating CD4+ CD8+ T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4+ CD8+ T cells in rhesus macaques. Two distinct populations of CD4+ CD8+ T cells were identified: the dominant one was CD4hi CD8lo and expressed the CD8,, homodimer, while the minor population was CD4lo CD8hi and expressed the CD8,, heterodimer. The majority of CD4hi CD8,lo T cells exhibited an activated effector/memory phenotype (CCR5lo CD7, CD28, HLA-DR+) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus-specific T cells was enriched five-fold in CD4hi CD8,lo T cells compared to single-positive CD4+ T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)-specific T cells. Cross-sectional studies of SIV-infected animals demonstrated that the frequency of CD4hi CD8,lo T cells was lower in wild-type SIV-infected animals compared to uninfected controls, although prospective studies of SIV-infected animals demonstrated depletion of CD4hi CD8,lo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4+ T cells expressing CD8, represent an effector/memory subset of CD4+ T cells and that this cell population can be depleted during the course of SIV infection. [source]


Fine-tuning CD4+ central memory T cell heterogeneity by strength of stimulation

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2008
Vandana Kalia
Abstract The memory T cell pool serves as a relatively long-lived heterogeneous repository of antigen-experienced T cells that "remember" previous encounters with antigen. While heterogeneity in the memory T cell pool is now well established, signals regulating the generation of this memory T cell heterogeneity are not fully understood. Two articles in this issue of the European Journal of Immunology highlight the importance of the strength of antigenic stimulation in regulating the generation of phenotypically and functionally distinct CD4+ T cell memory subsets. New insights are also provided into key molecular players that likely mediate differences in homeostatic and secondary expansion between the memory subsets. See accompanying articles: http://dx.doi.org/10.1002/eji200737611 and http://dx.doi.org/10.1002/eji200737852 [source]


Proliferative alloresponse of T-cytotoxic cells identifies rejection-prone children with steroid-free liver transplantation

LIVER TRANSPLANTATION, Issue 8 2009
Chethan Ashokkumar
Donor-induced and third-party,induced proliferation of T-helper and T-cytotoxic (Tc) cells and their naïve and memory subsets was evaluated simultaneously in single blood samples from 77 children who received steroid-free liver transplantation (LTx) after induction with rabbit anti-human thymocyte globulin. Proliferation was measured by dilution of the intravital dye carboxyfluorescein succinimidyl ester (CFSE) in a 3- to 4-day mixed lymphocyte response coculture. The ratio of donor/third-party,induced proliferated (CFSElow) T-cells was reported as the immunoreactivity index (IR) for each subset. Rejectors were defined as those who experienced biopsy-proven acute cellular rejection within 60 days of the assay. IR > 1 signified increased risk of rejection, and IR < 1 implied decreased risk. Demographics for 32 rejectors and 45 nonrejectors were similar. Proliferated CFSElow T-cells and subsets were significantly higher among rejectors compared with nonrejectors. In 33 of 77 randomly selected children, logistic regression, leave-one-out cross-validation, and receiver operating characteristic analyses showed that the IR of Tc cells was best associated with biopsy-proven rejection (sensitivity > 75%, specificity > 88%). Sensitivity and specificity were replicated in the remaining 44 children who composed the validation cohort. IR of CFSElow Tc cells correlated significantly with IR of proinflammatory, allospecific CD154+ Tc cells (r = 0.664, P = 0.0005) and inversely with IR of allospecific, anti-inflammatory, cytotoxic T lymphocyte antigen 4,positive Tc cells (r = ,0.630, P = 0.007). In conclusion, proliferative alloresponses of Tc cells can identify rejection-prone children receiving LTx. Liver Transpl 15:978,985, 2009. © 2009 AASLD. [source]


Contribution of Naïve and Memory T-Cell Populations to the Human Alloimmune Response

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009
C. Macedo
T-cell alloimmunity plays a dominant role in allograft rejection. The precise contribution of naïve and memory T cells to this response however remains unclear. To address this question, we established an ex vivo flow-cytometric assay that simultaneously measures proliferation, precursor frequency and effector molecule (IFN,, granzyme B/perforin) production of alloreactive T cells. By applying this assay to peripheral blood mononuclear cells from healthy volunteers, we demonstrate that the CD4+ and CD8+ populations mount similar proliferative responses and contain comparable frequencies of alloreactive precursors. Effector molecule expression, however, was significantly higher among CD8+ T cells. Analysis of sorted naïve and memory T cells showed that alloreactive precursors were equally present in both populations. The CD8+ effector and terminally differentiated effector memory subsets contained the highest proportion of granzyme B/perforin after allostimulation, suggesting that these cells present a significant threat to transplanted organs. Finally, we demonstrate that virus-specific lymphocytes contribute significantly to the alloresponse in certain responder,stimulator HLA combinations, underscoring the importance of T-cell cross-reactivity in alloimmunity. These results provide a quantitative assessment of the roles of naïve and memory T-cell subsets in the normal human alloimmune response and establish a platform for measuring T-cell alloreactivity pre- and posttransplantation. [source]