TY - JOUR
T1 - Central tolerance
T2 - What have we learned from mice?
AU - McCaughtry, Tom M.
AU - Hogquist, Kristin A.
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008/12
Y1 - 2008/12
N2 - Producing a healthy immune system capable of defending against pathogens, while avoiding autoimmunity, is dependent on thymic selection. Positive selection yields functional T cells that have the potential to recognize both self and foreign antigens. Therefore, negative selection exists to manage potentially self-reactive cells. Negative selection results from the induction of anergy, receptor editing, clonal diversion (agonist selection), and/or clonal deletion (apoptosis) in self-reactive clones. Clonal deletion has been inherently difficult to study because the cells of interest are undergoing apoptosis and being eliminated quickly. Furthermore, analysis of clonal deletion in humans has proved even more difficult due to availability of samples and lack of reagents. Mouse models have thus been instrumental in achieving our current understanding of central tolerance, and the evolution of elegant model systems has led to an explosion of new data to be assimilated. This review will focus on recent advances in the field of clonal deletion with respect to three aspects: the development of physiological model systems, signaling pathways that lead to apoptosis, and antigen presenting cell types involved in the induction of clonal deletion.
AB - Producing a healthy immune system capable of defending against pathogens, while avoiding autoimmunity, is dependent on thymic selection. Positive selection yields functional T cells that have the potential to recognize both self and foreign antigens. Therefore, negative selection exists to manage potentially self-reactive cells. Negative selection results from the induction of anergy, receptor editing, clonal diversion (agonist selection), and/or clonal deletion (apoptosis) in self-reactive clones. Clonal deletion has been inherently difficult to study because the cells of interest are undergoing apoptosis and being eliminated quickly. Furthermore, analysis of clonal deletion in humans has proved even more difficult due to availability of samples and lack of reagents. Mouse models have thus been instrumental in achieving our current understanding of central tolerance, and the evolution of elegant model systems has led to an explosion of new data to be assimilated. This review will focus on recent advances in the field of clonal deletion with respect to three aspects: the development of physiological model systems, signaling pathways that lead to apoptosis, and antigen presenting cell types involved in the induction of clonal deletion.
KW - Clonal deletion
KW - Thymus
KW - Tolerance
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U2 - 10.1007/s00281-008-0137-0
DO - 10.1007/s00281-008-0137-0
M3 - Review article
C2 - 19015857
AN - SCOPUS:57249095650
SN - 1863-2297
VL - 30
SP - 399
EP - 409
JO - Seminars in Immunopathology
JF - Seminars in Immunopathology
IS - 4
ER -