The Role of Intestinal Bacterial Flora in the Tuning of the T Cell Repertoire

Abstract

The role of the intestinal bacterial flora on the V β repertoire was examined using the gnotobiotic murine model. The ratio of V β6-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 V β6 in GF mice from 22.9% to 13.7%. In contrast, in BALB/c mice (Mls b) in which V β6 cells do not react with this endogenous superantigen, the ratio of V β6 cells do not react with this endogenous superantigen, the ratio of V β6 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 V β6 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 V β repertoire.