Downregulation of HLA class I antigen expression in CD4+ T lymphocytes from HIV type 1-infected individuals.
The expression of HLA class I antigens is downregulated in CD4+ T cells following in vitro HIV-1 infection. We determined whether the expression of HLA class I antigens is downmodulated in peripheral blood lymphocytes (PBLs) of HIV-1-positive subjects and whether this defect correlates with disease progression. A cohort of 62 HIV-1-seropositive individuals in different stages of disease was studied. Among these, four subjects were evaluated at yearly intervals for 6 years. The expression of HLA class I, HLA class II, and CD38 antigens was analyzed in PBLs and in CD4+ and CD8+ T lymphocyte subpopulations. The percentage of HLA class I-positive cells and the membrane density of HLA class I antigens were significantly lower in PBLs from HIV-1-positive individuals than in PBLs from HIV-negative controls, proportionally decreased with disease progression, and significantly correlated with the decrease in CD4+ T lymphocytes. Furthermore, the percentage of HLA class I-positive cells and the membrane density of HLA class I antigens were significantly lower in CD4+ T lymphocytes from AIDS patients with respect to CD4+ T lymphocytes from HIV-negative controls and to CD8+ T lymphocytes from HIV-negative controls and AIDS patients. By contrast, the expression of HLA class II and CD38 antigens was upregulated in CD4+ and CD8+ T lymphocytes from HIV-1-positive subjects. The defective expression of HLA class I antigens could impair the lysis of HIV-infected CD4+ cells by virus-specific HLA class I-restricted cytotoxic T lymphocytes and contribute to the progression of disease.
Puppo
F
F
Department of Internal Medicine, University of Genova, Italy.
Brenci
S
S
Bosco
O
O
Lanza
L
L
Barocci
S
S
Nocera
A
A
Ghio
M
M
Contini
P
P
Setti
M
M
Scudeletti
M
M
Indiveri
F
F
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male
D015395:Histocompatibility Antigens Class I