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.
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.
Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
L
L
Meyaard
S A
SA
Otto
B
B
Hooibrink
F
F
Miedema
D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male
D017252:CD3 Complex; D017493:Leukocyte Common Antigens