Abnormal expression of a 170-kilodalton P-glycoprotein encoded by MDR1 gene, a metabolically active efflux pump, in CD4(+) and CD8(+) T cells from patients with human immunodeficiency virus type 1 infection

Peripheral blood CD4(+) and CD8(+) T cells from 16 patients with HIV-1 infection, 8 each with CD4(+) T cell. counts of >200/mm(3) (group I) and with CD4(+) T cell counts of <200/mm(3) (group II), and 8 age- and sex-matched controls, were examined for the expression of P-glycoprotein (P-gp), a 170-kDa phosphoglycoprotein encoded by the MDR1 gene, using dual-color flow cytometric analysis, The function of P-glycoprotein was assessed by the accumulation of rhodamine-123 (Rh123) dye in the presence or absence of cyclosporin A (which inhibits Rh123 efflux). A significantly increased proportion of CD4+ T cells from patients with HIV-1 infection expressed P-glycoprotein as compared to controls, resulting in a significantly increased ratio of the proportions of CD4(+)P-gp(+)/CD8(+)P-gp(+) cells. The ratio of CD4(+)P-gp(+)/CDS+P-gp(+) in group II patients was significantly higher (p = 0.02) than in group I patients, suggesting a progressive increase in P-gp expression with the advancement of HIV-1 infection, The proportions of CD4(+)P-gp(+) and CD8(+)P-gp(+) T cells did not differ significantly between those who received AZT and those who were not treated with AZT, Contrary to expectation, both CD4(+) and CD8(+) T cells from patients accumulated significantly more Rh123 as compared to controls, Furthermore, cyclosporin A failed to increase intracellular accumulation of Rh123 in CD4+ and CD8(+) T cells from patients, These data suggest a functionally defective P-gp expression in HIV-1 infection that appears to increase with the progression of HIV-1 infection, A study of a large number of patients with HIV-1 infection is needed to determine the effects of opportunistic infection and antiretroviral therapy on the expression of P-gp and to determine whether the expression of P-gp could serve as another surrogate marker for the progression of HIV-1 infection.