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


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


CONCLUSIONS
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.
Funderburg
Nicholas
N
Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio, United States of America.
Luciano
Angel A
AA
Jiang
Wei
W
Rodriguez
Benigno
B
Sieg
Scott F
SF
Lederman
Michael M
MM
D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002453:Cell Cycle; D016923:Cell Death; D049109:Cell Proliferation; D005408:Flagellin / Q000378:metabolism; D006678:HIV / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D005408:Flagellin; D037181:Lectins, C-Type; D008024:Ligands; D008070:Lipopolysaccharides; D000099192:CD69 Antigens