Enhanced Interferon- gamma by CD8 super(+) CD28 super(-) Lymphocytes from HIV super(+) Patients

• Published in: Journal of clinical immunology 2001-03, Vol.21 (2), p.135-144
• Main Authors: Eylar, E H, Lefranc, C, Baez, I, Colon-Martinez, S L, Yamamura, Y, Rodriguez, N, Yano, N, Breithaupt, T B
• Format: Article
• Language: English
• Subjects: CD28 antigen; CD4 antigen; CD8 antigen; g-Interferon; Human immunodeficiency virus
• ISSN: 0271-9142

Flow cytometric analysis of T cells from HIV super(+) and normal individuals activated for 15 hr showed that the percentage of cells producing interferon- gamma (INF gamma ) was enhanced approximately threefold (39 compared to 14%) in the HIV super(+) CD8 super(+) population. Activation modes, other than anti-CD3 with PMA, were ineffective, and in no case did the percentage of HIV super(+) CD4 super(+) T cells show increased INF gamma production over controls. Enhanced INF gamma production was not induced by either anti-CD3 or PMA alone, or anti-CD3 or ConA with anti-CD28, or enhanced by N-acetylcysteine. In contrast to INF gamma production, the percentage of CD4 super(+) T cells producing interleukin-2 (Il-2) greatly exceeded that of the CD8 super(+) T cells. The results from flow cytometry analyses of HIV super(+) CD8 super(+) T cells was supported by quantitative analysis of INF gamma mRNA (by PCR) and INF gamma secretion by ELISA. These methods showed a sixfold and three- to fivefold increase, respectively, on a per cell basis. As HIV infection progresses, as shown by loss of CD4 super(+) T cells, the proportion of CD8 super(+) CD28 super(-) T cells increases, and it is this T cell subset that is responsible for 80% or more of the enhanced INF gamma production. The enhanced INF gamma in HIV super(+) patients derives from two factors: the increase in CD8 super(+) CD28 super(-) cells to 70% and the percentage producing INF gamma (60%, compared to 21% for CD8 super(+) CD28 super(+) cells). Our findings of a substantial increase in INF gamma production in HIV infection arising from the increased number of CD8 super(+) CD28 super(-) T cells are compatible with clinical studies which show elevated INF gamma in HIV super(+) serum and INF gamma producing CD8 super(+) T cells dominating HIV super(+) lymph nodes. We also found a significantly decreased proliferative response of the HIV super(+)-derived CD8 super(+) T cell fraction with coactivator anti-CD-28, in contrast to PMA (with anti-CD3), which is probably a reflection of the diminished population of CD8 super(+) CD28 super(+) T cells in HIV super(+) donors compared to normal donors (30.7 compared to 67.9%).