Fwm. Lu et al., Thymocyte resistance to glucocorticoids leads to antigen-specific unresponsiveness due to "holes" in the T cell repertoire, IMMUNITY, 12(2), 2000, pp. 183-192
We have proposed that glucocorticoids antagonize TCR-mediated activation an
d influence which TCR avidities result in positive or negative selection. W
e now analyze the immune response of mice whose thymocytes express antisens
e transcripts to the glucocorticoid receptor (TKO mice). TKO mice responded
normal ly to the complex antigen PPD but were proliferative nonresponders
to pigeon cytochrome c 81-104 (PCC), having a large decrease in the frequen
cy of PCC-responsive CD4(+) T cells. Unlike wild-type T cells, few TKO T ce
lls in PCC-specific cell lines expressed V alpha 11(+)V beta 3(+). Furtherm
ore, for naive CD4(+) T cells from unimmunized TKO mice, the frequencies of
many of the molecular features common to the CDR3 regions of PCC-responsiv
e V alpha 11(+)V beta 3(+) cells were substantially decreased. Thus, thymoc
yte glucocorticoid hyporesponsiveness resulted in loss of cells capable of
responding to PCC, corresponding to an antigen-specific "hole" in the T cel
l repertoire.