The Journal of Experimental Medicine
ImmunoPrecise
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© The Rockefeller University Press, 0022-1007/1998/9/1125/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 6, September 21, 1998 1125-1133

Articles

The Action of Bax and Bcl-2 on T Cell Selection

Owen Williams, Trisha Norton, Mark Halligey, Dimitris Kioussis, and Hugh J.M. Brady

From the Division of Molecular Immunology, Medical Research Council, National Institute for Medical Research, London NW7 1AA, United Kingdom

T cell development and selection in the thymus are shaped by the induction of apoptosis. However, a direct role in T cell development and selection for any of the molecules known to regulate apoptosis has remained controversial. We have studied the effect of bax and bcl-2 transgenes in recombination activation gene 1–deficient (RAG-1–/–) mice transgenic for the major histocompatibility complex class I–restricted F5 T cell receptor. Overexpression of a bax transgene in the thymus seriously impairs the production of mature T cells, whereas bcl-2 overexpression greatly promotes it. The effect of bax and bcl-2 overexpression on antigen-induced negative selection was studied using fetal thymic organ cultures. This analysis showed that Bcl-2 strongly inhibits negative selection, whereas Bax does not affect it. Our data directly show that Bcl-2 family members have specific roles in T cell selection and also lend support to the hypothesis that Bax and Bcl-2 can antagonize each other's action in a certain apoptosis pathway while in another they can be functionally nonreciprocal.

Key Words: Bax • Bcl-2 • thymic selection • apoptosis • fetal thymic organ cultures

Address correspondence to Hugh J.M. Brady, Division of Molecular Immunology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. Phone: 44-181-959-3666, ext. 2193; Fax: 44-181-913-8531; E-mail: h-brady{at}nimr.mrc.ac.uk

Abbreviations used: 7AAD, 7-aminoactinomycin; DP, double positive; FTOC, fetal thymic organ culture; NP, nucleoprotein; RAG-1, recombination activation gene 1; SP, single positive.


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