Enhanced interferon-γ by CD8+ CD28- lymphocytes from HIV+ patients

• Published in: Journal of clinical immunology Vol. 21; no. 2; pp. 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: Conference Proceeding Journal Article
• Language: English
• Published: New York, NY Kluwer/Plenum 01.03.2001
• Subjects: Adult; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Flow Cytometry; HIV Infections - immunology; HIV Infections - pathology; Human viral diseases; Humans; Infectious diseases; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Lymphocyte Count; Medical sciences; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Human; Immunopathology; Immune response; Pathophysiology; Immunophenotype; Cytokine; Retroviridae; AIDS; Immune deficiency; Lentivirus; Cell subpopulation; Infection; Virus; Immunological investigation; Viral disease; T-Lymphocyte; Human immunodeficiency virus; Gamma interferon
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1023/A:1011055805869

Flow cytometric analysis of T cells from HIV+ and normal individuals activated for 15 hr showed that the percentage of cells producing interferon-gamma (INFgamma) was enhanced approximately threefold (39 compared to 14%) in the HIV+ CD8+ population. Activation modes, other than anti-CD3 with PMA, were ineffective, and in no case did the percentage of HIV+ CD4+ T cells show increased INFgamma production over controls. Enhanced INFgamma 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 INFgamma production, the percentage of CD4+ T cells producing interleukin-2 (Il-2) greatly exceeded that of the CD8+ T cells. The results from flow cytometry analyses of HIV+ CD8+ T cells was supported by quantitative analysis of INFgamma mRNA (by PCR) and INFgamma 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+ T cells, the proportion of CD8+ CD28- T cells increases, and it is this T cell subset that is responsible for 80% or more of the enhanced INFgamma production. The enhanced INFgamma in HIV+ patients derives from two factors: the increase in CD8+ CD28- cells to 70% and the percentage producing INFgamma (60%, compared to 21% for CD8+ CD28+ cells). Our findings of a substantial increase in INFgamma production in HIV infection arising from the increased number of CD8+ CD28- T cells are compatible with clinical studies which show elevated INFgamma in HIV+ serum and INFgamma producing CD8+ T cells dominating HIV+ lymph nodes. We also found a significantly decreased proliferative response of the HIV+-derived CD8+ 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+ CD28+ T cells in HIV+ donors compared to normal donors (30.7 compared to 67.9%).