Quantitative Analysis of CD4+ T Cell Function in the Course of Human Immunodeficiency Virus Infection: Gradual Decline of Both Naive and Memory Alloreactive T Cells


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Abstract

Early in human immunodeficiency virus (HIV) infection CD4+ and CD8+ T cells are qualitatively affected.Loss of responses to recall antigen precedes impaired responses to allogeneic MHC and mitogens. The selective quantitative loss of memory T cells in early infection, only partially explains the observed defects. We investigated whether functional loss of T cells is preferentially observed for memory T cells or whether both naive and memory T cell subsets are affected in the course of HIV infection. We studied the proliferative response of CD4+ T cells from HIV-infected individuals to alloantigens, to which normally both naive and memory T cells respond, by limiting dilution analysis. The decreased proliferative response to alloantigens in HIV-infected individuals was associated with a decreased precursor frequency of alloreactive cells. The frequency was decreased in both the CD45RA+ (naive) and the CD45RO+ (memory) subset of CD4+ T cells. Analysis of four individuals in the course of HIV infection revealed similar kinetics of the decline in function in both subsets.Although initially T cell defects may be accounted for by the selective quantitative loss of memory cells, in later stages of HIV infection the function of both CD45RA+ and CD45RO+ cells is affected.(J. Clin. Invest. 1994. 94:1947-1952.) Key words: human immunodeficiency virus. T cells. immunopathogenesis. alloantigen. CD45RA/CD45RO antigens

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