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.