Abstract:
OBJECTIVE: To characterise, phenotypically, the CD8+ cell population involved in anti-HIV class-I MHC-restricted cytotoxic T cell (CTL) activity in HIV +ve individuals. METHODS: CTL activity was studied in 15 HIV +ve patients; 12/15 patients in CDC stage III and 3/15 patients in CDC stage IV. A 4 hour 51Chromium release assay was used. Autologous EBV transformed B cell lines infected with a vaccinia-HIVgag construct were incubated in vitro with cultured patient cells. Lymphocyte surface markers were determined on both whole blood and cultured lymphocytes, using a panel of monoclonal antibodies; HLA-DR, CD45RA (marker on immature T cells), CD29 and CD45RO (markers on mature T cells) CD57 (NK cells), and S6F1 (cytotoxic T cells). Cells were analysed by flow cytometry. RESULTS: Anti-HIVgag CTL activity was found in 8/12 of the CDC stage III patients and 0/3 of CDC stage IV group. The 7/15 patients with no detectable CTL activity had significantly reduced CD4 counts (P less than 0.005) when compared to the CTL +ve group. All patients had increased levels of CD8 cells co-expressing HLA-DR, CD45RO, CD29, S6F1 and CD57 when compared to controls. Analysis of in vitro cultured cells showed that CTL activity was found only in patients cells in which a significant increase in %CD8 CD45RO+ and HLA-DR+ cells (P less than 0.005) had occurred. CONCLUSION: Anti-HIVgag CTL activity is lost in the later stages of disease, and correlates with loss in CD4 cells. The loss of CTL activity was associated with an inability of CD8 CD45RO+ and HLA-DR+ cells to expand in vitro.
Keywords: Acquired Immunodeficiency Syndrome/*IMMUNOLOGY Antigens, CD/ANALYSIS Antigens, CD8/*ANALYSIS Comparative Study Cytotoxicity, Immunologic Gene Products, gag/*IMMUNOLOGY Human HIV Seropositivity/*IMMUNOLOGY HIV-1/*IMMUNOLOGY HLA-DR Antigens/ANALYSIS Lymphocyte Transformation T-Lymphocyte Subsets/*IMMUNOLOGY T-Lymphocytes, Cytotoxic/*IMMUNOLOGY ABSTRACT 921230
M92C4864
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