TY - JOUR
T1 - Inverse correlation between IL-7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulation
AU - Lang, Karl S.
AU - Recher, Mike
AU - Navarini, Alexander A.
AU - Harris, Nicola L.
AU - Löhning, Max
AU - Junt, Tobias
AU - Probst, Hans Christian
AU - Hengartner, Hans
AU - Zinkernagel, Rolf M.
PY - 2005/3/1
Y1 - 2005/3/1
N2 - 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-7Rα 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-7Rα expression, failed to induce T cell exhaustion, and primed T cells. Persistent antigen also suppressed IL-7Rα 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.
AB - 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-7Rα 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-7Rα expression, failed to induce T cell exhaustion, and primed T cells. Persistent antigen also suppressed IL-7Rα 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.
KW - Bcl-2
KW - Exhaustion
KW - Lymphocytic choriomeningitis virus
KW - Persistence
KW - Re-emergence
UR - http://www.scopus.com/inward/record.url?scp=15844411342&partnerID=8YFLogxK
U2 - 10.1002/eji.200425828
DO - 10.1002/eji.200425828
M3 - Article
C2 - 15724249
AN - SCOPUS:15844411342
VL - 35
SP - 738
EP - 745
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 3
ER -
