Inverse correlation between IL-7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulation.
Persistence is a hallmark of infection by viruses such as HIV, hepatitis B virus, hepatitis C virus and LCMV. In the case of LCMV, persistence may often be associated with exhaustion of CD8(+) T cells. We demonstrate here that persistent antigen suppressed IL-7Ralpha expression and this correlated with T cell exhaustion and reduced expression of the anti-apoptotic molecule B cell leukemia/lymphoma 2 (Bcl-2). In contrast, exposure to short-lived antigen only temporarily suppressed IL-7Ralpha expression, failed to induce T cell exhaustion, and primed T cells. Persistent antigen also suppressed IL-7Ralpha expression on primed T cells and this correlated with exhaustion of a previously stable primed T cell population. These findings suggest that antigen longevity regulates T cell fate.
Lang
Karl S
KS
Institute of Experimental Immunology, Zurich, Switzerland. karl.lang@usz.ch
Recher
Mike
M
Navarini
Alexander A
AA
Harris
Nicola L
NL
Löhning
Max
M
Junt
Tobias
T
Probst
Hans Christian
HC
Hengartner
Hans
H
Zinkernagel
Rolf M
RM
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D001117:Arenaviridae Infections / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis* / Q000276:immunology; D013997:Time Factors
D000956:Antigens, Viral; D019253:Proto-Oncogene Proteins c-bcl-2; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain