TCR LIGATION ON CD8-CELLS CREATES DOUBLE-NEGATIVE CELLS IN-VIVO( T)

The lack of CD95 in mice is associated with an accumulation of TCR alp ha beta(+) CD4(-)CD8(-) (double-negative (DN)) cells in the lymph node s (LNs) and other organs. To test the hypothesis that these DN cells a rise from TCR alpha beta(+)CD8(+) cells after activation via the TCR, we have crossed an MHC class I-restricted TCR transgene (tg) onto the lpr genotype to generate two TCR-transgenic experimental groups, TCRtg (+) lpr/+ (CD95-intact) and TCRtg(+) lpr/lpr (CD95-deficient), Specifi c peptide administration resulted in peripheral deletion of TCR alpha beta cells from the LNs of CD95-intact and CD95-deficient mice. On day 3 after peptide administration in the CD95-deficient but not the CD95 -intact mice, there was a ninefold increase in the percentage of DN ce lls in the LN; this increase returned to control levels by day 10, Per ipheral deletion was associated with an accumulation of TCR alpha beta (+)CD8(high) cells in the livers of mice of both genotypes by day 3, w hich returned to control levels by day 10 without an increase in the p ercentage or total number of DN cells. Our data show that the in vivo stimulation of TCR alpha beta(+)CD8(+) cells in the absence of CD95 re sults in an initial accumulation and an eventual loss of DN cells. Thi s identifies a role for CD95 after TCR alpha beta stimulation in the e fficient removal of TCR alpha beta(+)CD8(+) cells after the down-regul ation of CD8, CD95 is not essential for this process, because other me chanisms can compensate, but such mechanisms are less efficient in the LN.