COSTIMULATION OF T-CELL ACTIVATION AND VIRUS PRODUCTION BY B7-ANTIGENON ACTIVATED CD4-CELLS FROM HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1-INFECTED DONORS( T)

Infection with the human immunodeficiency virus type 1 (HIV-1) require s T-cell activation. Recent studies have shown that interactions of th e T-lymphocyte receptors CD28 and CTLA-4 with their counter receptor, B7, on antigen-presenting cells are required for optimal T-cell activa tion. Here we show that HIV-1 infection is associated with decreased e xpression of CD28 and increased expression of B7 on CD4+ T-cell lines generated from seropositive donors by alloantigen stimulation. Loss of CD28 expression was not seen on CD4+ T-cell lines from seronegative d onors, but up-regulation of B7 expression was observed upon more prolo nged culture. Both T-cell proliferation and interleukin 2 mRNA accumul ation in HIV-1-infected cultures required costimulation with exogenous B7 because these events were blocked by CTLA4Ig, a soluble form of CT LA-4 that binds B7 with high avidity. In contrast, levels of HIV-1 RNA were not affected by CTLA4Ig, indicating that regulation of virus tra nscription in these cultures did not depend upon CD28-B7 engagement. I nfected T cells could present alloantigen to fresh, uninfected CD4+ T cells, leading to increased proliferation and virus spread to the acti vated cells. Both of these events were blocked by CTLA4Ig. Thus, chron ic activation of HIV-1-infected CD4+ T cells reduces expression of CD2 8 and increases expression of B7, thereby enabling these T cells to be come antigen-presenting cells for uninfected CD4+ T cells; this might be another mechanism for HIV-1 transmission via T-cell-T-cell contact.