Polyclonal proliferation and apoptosis of CCR5+ T lymphocytes during primary human immunodeficiency virus type 1 infection: regulation by interleukin (IL)-2, IL-15, and Bcl-2. Export

@article{citeulike:3064291, abstract = {We measured apoptosis of subsets of T lymphocytes by single-cell analysis of caspase activation, to confirm high turnover of chemokine receptor CCR5(+) 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(+) 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-7, significantly inhibited caspase activation, increased Bcl-2 expression, and rapidly initiated proliferation in vitro of CD8(+) 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(+)Ki-67(+)Bcl-2(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(+) T cells will be important in understanding chronic HIV-1 replication and pathogenesis.}, address = {Centre for Immunology, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia.}, author = {Zaunders, J. J. and Moutouh-de Parseval, L. and Kitada, S. and Reed, J. C. and Rought, S. and Genini, D. and Leoni, L. and Kelleher, A. and Cooper, D. A. and Smith, D. E. and Grey, P. and Estaquier, J. and Little, S. and Richman, D. D. and Corbeil, J.}, citeulike-article-id = {3064291}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/12751031}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=12751031}, day = {1}, issn = {0022-1899}, journal = {The Journal of infectious diseases}, keywords = {chemo\_receptor, hiv-1, tania\_tb\_paper}, month = {June}, number = {11}, pages = {1735--1747}, posted-at = {2008-07-30 23:44:09}, priority = {2}, title = {Polyclonal proliferation and apoptosis of CCR5+ T lymphocytes during primary human immunodeficiency virus type 1 infection: regulation by interleukin (IL)-2, IL-15, and Bcl-2.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/12751031}, volume = {187}, year = {2003} }

TY - JOUR ID - citeulike:3064291 L3 - citeulike-article-id:3064291 N2 - We measured apoptosis of subsets of T lymphocytes by single-cell analysis of caspase activation, to confirm high turnover of chemokine receptor CCR5(+) 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(+) 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-7, significantly inhibited caspase activation, increased Bcl-2 expression, and rapidly initiated proliferation in vitro of CD8(+) 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(+)Ki-67(+)Bcl-2(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(+) T cells will be important in understanding chronic HIV-1 replication and pathogenesis. IS - 11 JF - The Journal of infectious diseases SN - 0022-1899 AD - Centre for Immunology, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia. EP - 1747 TI - Polyclonal proliferation and apoptosis of CCR5+ T lymphocytes during primary human immunodeficiency virus type 1 infection: regulation by interleukin (IL)-2, IL-15, and Bcl-2. VL - 187 SP - 1735 KW - chemo_receptor KW - hiv-1 KW - tania_tb_paper AU - Zaunders, JJ AU - Moutouh-de Parseval, L AU - Kitada, S AU - Reed, JC AU - Rought, S AU - Genini, D AU - Leoni, L AU - Kelleher, A AU - Cooper, DA AU - Smith, DE AU - Grey, P AU - Estaquier, J AU - Little, S AU - Richman, DD AU - Corbeil, J PY - 2003/06/01/ UR - http://view.ncbi.nlm.nih.gov/pubmed/12751031 ER -