Functional and phenotypic evidence for a selective loss of memory T cells in asymptomatic human immunodeficiency virus-infected men.
In addition to a well-documented depletion of CD4+ T helper cells in later stages of human immunodeficiency virus (HIV) infection, evidence has been provided for a specific unresponsiveness to triggering either by specific antigen in the context of autologous major histocompatibility molecules (self + X) or anti-CD3 monoclonal antibodies (MAb) in both CD4 and CD8 cells from asymptomatic HIV-infected individuals. In the present study we analyzed this unresponsiveness using mitogenic antibodies to distinct T cell membrane receptors. T cells from HIV-infected men who had normal numbers of CD4+ T cells responded poorly to activation signals via the CD3 membrane antigen in both accessory cell-dependent as well as accessory cell-independent culture systems. A similar low response was observed in an anti-CD2-driven system. In contrast, proliferation induced by anti-CD3, anti-CD2, or the phorbol ester Phorbol myristate acetate could be normally enhanced by anti-CD28 MAb. We demonstrated that this unresponsiveness is not due to a failure to induce early events required for activation, such as increased intracellular concentration of free calcium and activation of protein kinase C, but is caused by an imbalance between naive and memory T cells. In HIV-infected asymptomatic men, CD29+ memory T cells are selectively depleted which results in a poor responsiveness to self + X. These findings provide new insights that may have implications for our understanding of the immunopathogenesis of AIDS.
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
C J
CJ
van Noesel
R A
RA
Gruters
F G
FG
Terpstra
P T
PT
Schellekens
R A
RA
van Lier
F
F
Miedema
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D002118:Calcium / Q000502:physiology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D019012:Integrin beta1; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D019012:Integrin beta1; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D017493:Leukocyte Common Antigens; D002118:Calcium