HOMING OF TRANSGENIC GAMMA-DELTA T-CELLS INTO MURINE VAGINAL EPITHELIUM

The vaginal epithelium of normal mice contains lymphocytes of fetal th ymic origin that express an invariant V(gamma)4/V(delta)1 TCR, The app arent lack of other gamma delta TCR species suggests that a selection mechanism might operate to regulate the localization of gamma delta T cells at this anatomical site. Selection might be connected to the V(g amma)4/V(delta)1 TCR or to some homing characteristic of the fetal thy mic lineage that appears at day 17-18 of embryonic life. In the presen t studies, we investigated whether transgenic gamma delta cells expres sing a TCR species characteristic of the subpopulation of gamma delta T cells found in the blood, spleen and lymph would translocate to the vaginal epithelium. We found that the transgenic V(gamma)2 TCR+ cells did accumulate in the vagina of transgenic mice. Furthermore, like nor mal vaginal gamma delta T cells, the transgenic vaginal gamma delta T cells expressed the phenotype of recently activated memory/effector T cells (CD44(hi), CD62L(-), CD45RB(lo), CD69(+)). Vaginal gamma delta T cells in normal mice do not express the CD2 and CD28 antigens, but bo th of these markers are present on transgenic vaginal gamma delta T ce lls. We observed that a small fraction of splenic transgenic gamma del ta T cells had the same surface phenotype as the vaginal transgenic ga mma delta T cells, raising the possibility that the gamma delta T cell s present in the vaginal epithelium of transgenic mice originated from the peripheral lymphoid organs. Data in support of this possibility c ame from experiments in which co-incubation of splenic transgenic gamm a delta T cells with vaginal epithelial cell suspensions induced the v aginal gamma delta phenotype on the splenic gamma delta T cells. The f inding of transgenic gamma delta T cells in the vaginal epithelium sug gests that homing of gamma delta T cells to this site is not restricte d to gamma delta T cells that express the V(gamma)4/V(delta)1 invarian t TCR, Furthermore, these findings imply that retention of gamma delta T cells in the vaginal epithelium of normal mice is affected by a V(g amma)4/V(delta)1-specific mechanism. The finding of a significant leve l of apoptosis in the transgenic vaginal gamma delta T cells, but not in the normal vaginal gamma delta T cells, could reflect that the mech anism of retention of V(gamma)4/V(delta)1(+) in the vaginal epithelium involves selective survival at the site.