HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION OF CD4(-CELLS DOWN-REGULATES THE EXPRESSION OF CD28 - EFFECT ON T-CELL ACTIVATION AND CYTOKINE PRODUCTION() T)

Infection with human immunodeficiency virus type 1 (HIV-1) results in dysregulation of normal T cell function. To study the effects of HIV-1 at the cellular level, primary T cell lines were generated by alloant igen stimulation of CD4(+) T cells collected from peripheral blood of HIV-1-infected donors. Using Epstein-Barr virus-infected B lymphocytes (EBV-LCL) as a source of alloantigen, the T cell lines were expanded in vitro for 7 weeks. Uninfected T cell lines were cultured in paralle l. Virus was inducible from the infected lines with stimulation, and c omplete infection was achieved after 4-7 weeks depending on the line. The downmodulation of CD28 expression correlated with virus replicatio n and spread. Furthermore, CD28 mRNA was not inducible in the infected lines after stimulation with alloantigen. Loss of CD28 correlated wit h reduced responsiveness to costimulation with a monoclonal antibody t o CD28 following similar engagement of the CD3 protein. In contrast, a ctivation with alloantigen was not affected. HIV-1 infection and down- modulation of CD28 did not alter the relative levels of IL-2, IFN-gamm a, and IL-4 mRNA. Production of the various cytokine mRNAs following a lloantigen stimulation was inhibited by CTLA4Ig and thus remained unde r the regulation oft CD80 and CD86 expressed on the EBV LCL. Taken tog ether, our data suggest that dysregulation of normal T cell function a ssociated with HIV-1 infection may result in part from the loss of CD2 8 expression. (C) 1995 Academic Press, Inc.