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Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):210-4. Epub 2003 Dec 23.

Thymic selection can compensate for mutations affecting T cell activation and generate a normal T cell repertoire in mutant mice.

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  • 1Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.


Thymic selection adjusts the reactivity of the peripheral T cell repertoire to maximize recognition of pathogens and minimize stimulation by innocuous substances and self-antigen. The study of molecules implicated in T cell activation often involves the generation of knockout (-/-) mice. In many instances, knockout animals display revealing phenotypes. But should a lack of phenotype be interpreted as a lack of function? Bcl-xgamma was shown previously to affect T cell activation in vitro, and here we note that overexpression of this molecule increases cell cycling after T cell receptor ligation by antibody. It was therefore surprising that Bcl-xgamma(-/-), Bcl-xgamma transgenic, and WT T cells displayed similar levels of sensitivity to antigen according to ex vivo stimulation. Bcl-xgamma could be demonstrated to influence competitiveness and selection of thymocytes in a manner that counteracted the effects of Bcl-xgamma mutation on T cell activation. These findings suggest that thymic selection can overcome genetic defects in T cell activation to generate a T cell repertoire of normal reactivity.

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