Control of T lymphocyte signal transduction through clonal anergy

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
P FieldsThomas F Gajewski

Abstract

Stimulation of interleukin-2 producing T lymphocytes via the T cell receptor (TCR) complex in the absence of other costimulatory factor results paradoxically not in activation but in an unresponsive state termed clonal anergy. T cell anergy appears to be a mechanism by which potentially autoreactive T lymphocytes are inactivated in the periphery, thus maintaining tolerance to self antigens. The breakdown of such tolerance may result in autoimmune diseases. In contrast, induction of peripheral tolerance is the ultimate goal in organ transplantation and is a potential mechanism by which a growing tumor evades immune destruction. The anergic state is characterized by an inability to secrete interleukin-2 and proliferate following restimulation via the TCR even in the presence of constimulatory factors. Recent studies have demonstrated a specific block in Ras activation in anergic T lymphocytes. This defect is correlated with a failure to activate the downstream effectors Erk and Jnk and a lack of activation of the AP-1 transcription factor complex, offering a plausible mechanism for the inability to initiate interleukin-2 gene transcription in the anergic state.

Citations

Oct 10, 2006·Nature Immunology·Yuanyuan ZhaThomas F Gajewski
Feb 15, 2002·British Journal of Haematology·F VuillierD Scott-Algara
Nov 7, 2012·The Journal of Experimental Medicine·Yan ZhengThomas F Gajewski
Dec 4, 2003·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Masaharu Shin-YaMinoru Takeuchi
Apr 20, 2004·Assay and Drug Development Technologies·Christopher J HoweRichard A Franklin
Nov 10, 2005·Arthritis Research & Therapy·Jody L BonnevierDaniel L Mueller
Sep 4, 2003·Leukemia & Lymphoma·Françoise Vuillier, Guillaume Dighiero
Jan 5, 2008·EMBO Reports·Yan ZhengThomas F Gajewski
Sep 16, 2006·Immunological Reviews·Thomas F GajewskiHelena Harlin
Aug 15, 2002·Cell·Mark M Davis
May 16, 2006·Journal of Immunotherapy·Thomas F GajewskiHelena Harlin
Jun 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Todd N EagarStephen D Miller
Sep 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thomas F Gajewski
Sep 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gregory LizéePatrick Hwu
Aug 9, 2007·Science's STKE : Signal Transduction Knowledge Environment·Binks W Wattenberg, Daniel M Raben

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