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.
Keywords: Animals ; Antigens, Viral/*immunology ; Apoptosis/immunology ; Arenaviridae Infections/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Flow Cytometry ; Lymphocytic choriomeningitis virus/*immunology ; Mice ; Proto-Oncogene Proteins c-bcl-2/biosynthesis ; Receptors, Interleukin-7/*biosynthesis/immunology ; Time Factors
Lang, Karl S Recher, Mike Navarini, Alexander A Harris, Nicola L Lohning, Max Junt, Tobias Probst, Hans Christian Hengartner, Hans Zinkernagel, Rolf M Research Support, Non-U.S. Gov't Germany European journal of immunology Eur J Immunol. 2005 Mar;35(3):738-45.
Record created on 2010-01-06, modified on 2016-08-08