ABSTRACT
The relationship between T cell activation and human immunodeficiency virus type 1 (HIV-1) replication was studied in HIV-infected subjects, 20 with and 10 without anti-HIV treatment. Expression of Ki-67 proliferation-associated antigen was increased in CD4+ and CD8+ T cells and correlated with HLA-DR. In subjects without anti-HIV treatment, the plasma HIV-1 RNA level correlated with HLA-DR in CD4+ T cells, with Ki-67 in CD8+ T cells, and with expression of CD38 in both T cell subsets. A proportion of treated subjects had increased T cell activation despite 4 months of highly active antiretroviral treatment (HAART). In subjects receiving HAART, a high percentage of HLA-DR+ CD4+ T cells was associated with signs of opportunistic infections. This work supports the concept that, in the natural course of HIV-1 infection, HIV replication itself leads to general T cell activation and that opportunistic infections generate additional CD4+ T cell activation and HIV replication.
Subject(s)
Antigens, CD , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , HIV Antigens/analysis , HIV Infections/immunology , HIV-1/growth & development , RNA, Viral/blood , Virus Replication/immunology , ADP-ribosyl Cyclase , ADP-ribosyl Cyclase 1 , Adult , Antigens, Differentiation/analysis , Biomarkers , HIV Infections/virology , Humans , Ki-67 Antigen/analysis , Lymphocyte Activation , Membrane Glycoproteins , Middle Aged , NAD+ Nucleosidase/analysis , beta 2-Microglobulin/analysisABSTRACT
The frequencies of human immunodeficiency virus type 1 (HIV-1) Gag- and Epstein-Barr virus (EBV)-specific cytotoxic T lymphocyte precursors (CTLp) were studied longitudinally in peripheral blood mononuclear cells from 9 HIV-1-infected persons. By antigen-specific stimulation, HIV-1 Gag-specific CTLp were detected in vitro throughout the course of HIV-1 infection, even after the onset of overt disease. In 4 patients, however, HIV-1 Gag-specific CTLp frequencies declined over time in the presence of maintained EBV-specific CTLp. This decline was correlated with decreasing CD4 (r = .38; P < .05) and CD8 (r = .75; P < .001) cell numbers. The maintenance of EBV-specific CTLp in patients with low CD4 cell numbers indicated that EBV-specific CTL-mediated immunity may remain longer unaffected by HIV-1-induced immune dysfunction. Consistent with this observation, the growth of EBV-specific CTL could be supported in vitro by EBV-infected lymphoblastoid B cell lines, independent of both CD4 cells and exogenous cytokines.
