Conservation of total T-cell counts during HIV infection: alternative hypotheses and implications.
While CD4+ T-cell counts in the blood of HIV-infected individuals gradually decrease, there is a parallel increase in the number of blood CD8+ T cells such that the total number of T cells remains essentially constant for several years (1). The basis and significance of this phenomenon are not known. Based on a statistical analysis of longitudinal T-cell counts from the Transfusion Safety Study (TSS) database and on theoretical considerations, we evaluate several alternative models, including versions of the "blind homeostasis" (BH) hypothesis (1-3). At issue is the nature of the homeostatic regulation of lymphocytes and its apparent failure in HIV infection. The most plausible explanation for the conservation of total blood T-cell numbers while subset ratios change is that CD4+ and CD8+ T cells compete for a limited access to the blood compartment. Such interaction between the subsets implies, in particular, that changes in the number of CD4+ T cells occurring in other tissues cannot be reliably inferred from those observed in the blood. We reiterate propositions made earlier (4) that much of the apparent "depletion" of CD4+ lymphocytes during the asymptomatic phase of HIV infection may be attributed to redistribution between the tissues and the blood compartment.
Grossman
Z
Z
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv, Israel.
Herberman
R B
RB
Vatnik
N
N
Intrator
N
N
D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015658:HIV Infections / Q000097:blood* / Q000276:immunology / Q000821:virology; D006706:Homeostasis; D006801:Humans; D018655:Lymphocyte Count; D008954:Models, Biological; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*