T-cell homeostasis: implications in HIV infection .
Evidence is presented that a homeostatic mechanism exists that maintains a normal T-cell count, but is unresponsive to abnormalities in CD4+ T-cell count and CD8+ T-cell count. Specifically, we hypothesize that in all cases of T-cell loss, whether selective or not, both CD4+ T cells and CD8+ T cells will be produced until the absolute T-cell count returns to normal, even if this produces or exacerbates abnormalities in the absolute CD4+ T-cell count and absolute CD8+ T-cell count. This hypothesis implies that the selective loss of CD4+ T cells will induce the production of both CD4+ T cells and CD8+ T cells with the result that T-cell count will return to normal, but a persistent CD8+ T-cell lymphocytosis and CD4+ T-cell lymphopenia will be produced. To test this hypothesis, we monitored T-cell reconstitution in mice selectively depleted of CD4+ T cells through treatment with a CD4-specific monoclonal antibody (mAb). Consistent with our hypothesis, the absolute peripheral blood T-cell count in treated mice returned to that of controls after approximately 4 months. However, the absolute CD8+ cell count became 163% of controls and the absolute CD4+ cell count remained less than 63% of controls. Our hypothesis may have implications regarding the pathogenesis and treatment of human immunodeficiency virus (HIV) infection. In particular, the hypothesis implies that the unresolved CD4+ T-cell lymphopenia seen in the first several years of HIV infection is the "natural" consequence of the interaction of a selective CD4+ T-cell depleting virus and a nonselective T-cell replacing homeostatic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
Adleman
L M
LM
Department of Medicine, University of California, San Francisco.
Wofsy
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D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood* / Q000276:immunology; D006706:Homeostasis / Q000502:physiology*; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal