Down-modulation of MHC-I in a CD4+ T cell line, CEM-E5, after HIV-1 infection.

HIV-1 is capable of infecting many different cell types that express the CD4 molecule. In vivo and in vitro this infection is associated with profound immunologic defects. We have examined the effect of HIV-1 infection on the expression of MHC class I (MHC-I) molecules to explore the possibility that this important immune system molecule is perturbed after HIV-1 infection. Our data show that in vitro, HIV-1 infection of CD4+ PBL, and the CD4+ cell lines, CEM-E5, HT, and U937, results in decreased expression of MHC-I molecules on the cell surface. This down-modulation is transient, occurring 18 h after HIV-1 infection of CD4+ PBL and returning to normal expression by 24 h. In CEM-E5, MHC-I down-modulation occurs over the course of days, reaching its greatest decrease (40%) about the time the cells are producing the most virus. Reversal of MHC-I expression to normal levels occurs as viral production decreases. Down-regulation during the time periods examined appear to be specific for MHC-I and does not occur with other cell-surface Ag nor is it caused by selection of a preexisting cell population with low MHC-I expression. Radioimmunoprecipitation of MHC-I protein from CEM-E5 indicated that the decrease of surface MHC-I is caused by decreased total protein secondary to a decrease in the level of mRNA for MHC-I. These decreased levels of MHC-I are biologically relevant because HIV-1 infected CEM-E5 cells are less susceptible to CTL lysis determined by the use of MHC-I cytolytic T cell clones and with the use of cold target-inhibition assay.