Toll-like receptor ligands induce human T cell activation and death, a model for HIV pathogenesis.

TitleToll-like receptor ligands induce human T cell activation and death, a model for HIV pathogenesis.
Publication TypeJournal Article
Year of Publication2008
AuthorsFunderburg N, Luciano AA, Jiang W, Rodriguez B, Sieg SF, Lederman MM
JournalPLoS One
Volume3
Issue4
Paginatione1915
Date Published2008
ISSN1932-6203
KeywordsAntigens, CD, Antigens, Differentiation, T-Lymphocyte, Apoptosis, CD4-Positive T-Lymphocytes, Cell Cycle, Cell Death, Cell Proliferation, Flagellin, HIV, HIV Infections, Homeostasis, Humans, Lectins, C-Type, Leukocytes, Mononuclear, Ligands, Lipopolysaccharides, T-Lymphocytes
Abstract

BACKGROUND: Recently, heightened systemic translocation of microbial products was found in persons with chronic HIV infection and this was linked to immune activation and CD4(+) T cell homeostasis.

METHODOLOGY: We examined here the effects of microbial Toll-like receptor (TLR) ligands on T cell activation in vitro.

CONCLUSIONS/FINDINGS: We show that exposure to TLR ligands results in activation of memory and effector CD4(+) and CD8(+) T cells. After exposure to each of 8 different ligands that activate TLRs 2, 3, 4, 5, 7, 8, and 9, CD8(+) T cells are activated and gain expression of the C type lectin CD69 that may promote their retention in lymphoid tissues. In contrast, CD4(+) T cells rarely increase CD69 expression but instead enter cell cycle. Despite activation and cell cycle entry, CD4(+) T cells divide poorly and instead, disproportionately undergo activation-induced cell death. Systemic exposure to TLR agonists may therefore increase immune activation, effector cell sequestration in lymphoid tissues and T cell turnover. These events may contribute to the pathogenesis of immune dysfunction and CD4+ T cell losses in chronic infection with the human immunodeficiency virus.

DOI10.1371/journal.pone.0001915
Alternate JournalPLoS ONE
PubMed ID18382686
PubMed Central IDPMC2271052
Grant ListAI 36219 / AI / NIAID NIH HHS / United States
AI 38858 / AI / NIAID NIH HHS / United States