Polyclonal Proliferation and Apoptosis of CCR5 super(+) T Lymphocytes during Primary Human Immunodeficiency Virus Type 1 Infection: Regulation by Interleukin (IL)-2, IL-15, and Bcl-2

• Published in: The Journal of infectious diseases 2003-06, Vol.187 (11), p.1735-1747
• Main Authors: Zaunders, J J, Moutouh-De Parseval, L, Kitada, S, Reed, J C, Rought, S, Genini, D, Leoni, L, Kelleher, A, Cooper, DA, Smith, DE, Grey, P, Estaquier, J, Little, S, Richman, D D, Corbeil, J
• Format: Article
• Language: English
• ISSN: 0022-1899

We measured apoptosis of subsets of T lymphocytes by single-cell analysis of caspase activation, to confirm high turnover of chemokine receptor CCR5 super(+) T cells in subjects with acute, primary human immunodeficiency virus type 1 (HIV-1) infection (PHI). High levels of spontaneous apoptosis, consisting mainly of CD8 super(+) T lymphocytes, were closely associated with increases in the activation markers Ki-67, CD38, and the HIV coreceptor CCR5 and with decreases in Bcl-2 and the interleukin (IL)-7 receptor at the single-cell level. Increased expression of Ki-67 and CCR5 ex vivo, as well as increased apoptosis, was seen in all T cell receptor beta -chain variable region (TCRBV) subfamilies studied. The addition of IL-2 or IL-15, but not IL-17, significantly inhibited caspase activation, increased Bcl-2 expression, and rapidly initiated proliferation in vitro of CD8 super(+) T cells expressing CCR5 and multiple TCRBV subfamilies. Furthermore, IL-15 receptor alpha -chain messenger RNA levels were increased in peripheral blood mononuclear cells during PHI. These results suggest that CCR5 super(+)Ki-67 super(+)Bcl-2 super(dim) activated T cells generated during PHI traffic via blood to tissue sites, where the cells may survive and/or further proliferate under the local influence of IL-2 or IL-15. Understanding cytokine effects on CCR5 super(+) T cells will be important in understanding chronic HIV-1 replication and pathogenesis.