INVITRO STUDIES OF HIV-1 EXPRESSION IN THYMOCYTES FROM INFANTS AND CHILDREN

Objective: To determine whether thymocytes from infants and young children can be infected with and their maturation capability altered by HIV-1, and to examine the effects of interleukin (IL)-2 and IL-4 on this process. Design: Serum-free culture medium was used so that cytokine effects could be studied under defined conditions. The primary virus isolates HIV-1JR-CSF and HIV-1JR-FL were used because their effects should most closely resemble those of viruses which might be found in an infected child. Methods: Thymocytes from infants and young children were infected with virus and cultured in serum-free medium with the cytokines IL-2 and IL-4 alone or in combination. HIV-1 expression was measured after 12 days by p24 levels in culture supernatants. Thymocyte maturation was determined by changes in surface phenotype, as measured by flow cytometry. Results: HIV-1 expression by thymocytes, which increased with time of culture, occurred when thymocytes were cultured with each cytokine. p24 levels were slightly increased when cultured with IL-2, compared with IL-4. Virus expression was remarkably increased when the cytokines were combined in culture. This expression was synergistic rather than additive. The synergy, evident in mature, but not immature thymocytes, was demonstrated with both pharmacologic and physiologic concentrations of cytokines. T-cells from peripheral blood cultured under the same conditions demonstrated lower virus expression in the presence of cytokines and synergy was not shown. Cytokine-induced thymocyte maturation and thymocyte survival in vitro was unimpaired by infection with HIV-1. Conclusions: These findings indicate that the cytokines IL-2 and IL-4, which are normally present in the thymic environment, can synergize to promote HIV-1 expression by thymocytes infected in vitro. This occurs without impairing the maturation induced by these cytokines. Thus, the mature thymocyte may provide a continuous supply of virus-expressing T-cells to the peripheral blood and lymphoid tissues of the infected child.