The central defect in AIDS is a loss of T4 cells. Current treatment protocols have not been able to reverse this decline and as a result they do not enhance survival. We suggest the lack of an effective treatment is due to fact that the pathogenesis of AIDS following HTLV-III infection and in particular the mechanism for the massive loss of T cells is not clear. The decline in T4 cells is reflected in an increasing inability of cells from patients to form T cell colonies in agar (CFU-T). We propose to use this CFU-T assay to inverigate mechanisms for the loss of T cells and treatment strategies to reverse this loss. We have documented a significant decrease in CFU -T formation in lymphadenopathy (LAS)S patients which becomes more pronounced in AIDS. This is due in part to a lack of precursor cells, the presence of suppressor cells and suppressive factors. These defects can be partially reversed by the in vitro addition of certain modulators such as phosphonoformate and thymosin fraction 5, but not by others such as interleuklin-2 and interferon. We propose to continue investigations into the nature of the differentiation defect and its relation to the in vivo loss of T cells. We suggest the loss of a small number of infected T cells would not lead to the overall decline in T cell number without a concomitant block in differentiation which prevents their replacement. In particular we will investigate the role of HTLV-III and other viral co-factors in this process. We will further continue to test compounds for their ability to modulate colony formation. These in vitro tests will be carried out in parallel to in vivo clinical trials. It is possible that the in vitro assay can be used to predict which drug or combination of drugs will contribute to a reconstitution of T cell numbers in vivo, and identify those individuals most likely to benefit from a particular treatment.
| Wu, J; Levy, E M; Black, P H (1989) 2-Mercaptoethanol and n-acetylcysteine enhance T cell colony formation in AIDS and ARC. Clin Exp Immunol 77:7-10 |
| Levy, E M; Wu, J M; Cohn, S E et al. (1989) Increased T-cell colony formation in AIDS patients treated with zidovudine: a possible mechanism for increased lymphocyte number. AIDS 3:605-7 |
