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HIV infection reduces the T-cell regeneration capacity of human peripheral blood in an organ culture system.




 

Int Conf AIDS. 1996 Jul 7-12;11(2):9 (abstract no. We.A.264). Unique

Objective: Infection with the human immunodeficiency virus is characterized by depletion of CD4+ T cells. In the past, it has been difficult to determine the effects of HIV infection on the development of the T-cell lineage. We have examined the ability of human peripheral blood from HIV-infected patients to regenerate T-cells using a unique chimeric organ culture system. Methods: Approximately 1 x 105 peripheral blood mononuclear cells from 16 HIV-infected patients (CD4 count from 20 - 1072/microliter) and 8 control subjects were placed on NOD/LtSz-scid/scid fetal thymus lobes in organ culture. Cells were cultured for 12d and subsequently stained with antibody against T-lymphocyte surface antigens and analyzed by flow cytometry. Culture supernatants were analyzed for reverse transcriptase activity (RT) to assess for viral replication in culture. Results: In all cases, the total number of lymphocytes generated from the HIV-infected patients was at least 3-fold fewer than in the controls. In addition, the number of CD4+ and CD4/CD8 double-positive cells from patients was always below those of control by at least 3-fold. The number of CD8 cells regenerated in vitro from patients was variable. There was no relationship between the number of regenerating CD4 or CD4/CD8-positive cells in vitro and the patients' peripheral blood CD4 count, nor to RT activity in cultured supernatants. Addition of zidovudine (1 and 10 micrograms/ml) to the culture did not change the regenerative ability of cells from either the patients or the controls. Moreover, regenerative ability of cells from patients was not associated with whether the patient was taking antiretroviral therapy or not. Conclusions: Regardless of peripheral blood CD4 count or RT activity, regeneration of CD4 and CD4/CD8 lymphocytes in vitro by HIV-infected patients is diminished. Since murine recipient tissue was used in this study, the effect of HIV on the thymic microenvironment has been minimized, suggesting that this defect resides in prethymocytes.

*CD4 Lymphocyte Count *CD4-Positive T-Lymphocytes/PHYSIOLOGY *CD8-Positive T-Lymphocytes/PHYSIOLOGY *HIV Infections/PATHOLOGY



 




Information in this article was accurate in January 30, 1997. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.