The role of intestinal bacterial flora in the tuning of the T cell repertoire.

The role of the intestinal bacterial flora on the Vbeta repertoire was examined using the gnotobiotic murine model. The ratio of Vbeta6-positive T cells in the periphery of DBA/2 mice under SPF conditions was only 2.2% (mean, n = 4), since the cells were eliminated by the endogenous superantigen Mls(a). However, the ratio in germ-free (GF) mice was 31.7%. Similarly, the contamination of the GF Mice with the intestinal flora from SPF mice reduced the ratio of Vbeta6 in GF mice from 22.9% to 13.7%. In contrast, in BALB/c mice (Mls(b)) in which Vbeta6 cells do not react with this endogenous superantigen, the ratio of Vbeta6 cells do not react with this endogenous superantigen, the ratio of Vbeta6 of SPF mice (15.4%, mean, n = 3) was found to be comparable to that of GF mice (15.6%, n = 3). These data suggested that the absence of intestinal flora deteriorated a part of the Mls(a) determinant, which reacted with the Vbeta6 T cells and thereby eliminated them, thus resulting in an increase of these cells in GF mice. Moreover, the alloantigenicity of minor histocompatible alloantigen(s) (mHAg) in SPF mice, which was detected in H-2 identical MLR experiments and a murine graft-versus-host (GVH) model, was reduced in GF and decontaminated SPF mice, thus indicating that the intestinal flora upregulated the mHAg including a part of Mls determinant. These results therefore suggest that the intestinal flora plays a role in the upregulation of mHAg including a part of endogenous superantigen and the consequent tuning of the Vbeta repertoire.