Homing of transgenic gammadelta T cells into murine vaginal epithelium.
The vaginal epithelium of normal mice contains lymphocytes of fetal thymic origin that express an invariant Vgamma4/Vdelta1 TCR. The apparent lack of other gammadelta TCR species suggests that a selection mechanism might operate to regulate the localization of gammadelta T cells at this anatomical site. Selection might be connected to the Vgamma4/Vdelta1 TCR or to some homing characteristic of the fetal thymic lineage that appears at day 17-18 of embryonic life. In the present studies, we investigated whether transgenic gammadelta cells expressing a TCR species characteristic of the subpopulation of gammadelta T cells found in the blood, spleen and lymph would translocate to the vaginal epithelium. We found that the transgenic Vgamma2 TCR+ cells did accumulate in the vagina of transgenic mice. Furthermore, like normal vaginal gammadelta T cells, the transgenic vaginal gammadelta T cells expressed the phenotype of recently activated memory/effector T cells (CD44(hi), CD62L-, CD45RB(lo), CD69+). Vaginal gammadelta T cells in normal mice do not express the CD2 and CD28 antigens, but both of these markers are present on transgenic vaginal gammadelta T cells. We observed that a small fraction of splenic transgenic gammadelta T cells had the same surface phenotype as the vaginal transgenic gammadelta T cells, raising the possibility that the gammadelta T cells present in the vaginal epithelium of transgenic mice originated from the peripheral lymphoid organs. Data in support of this possibility came from experiments in which co-incubation of splenic transgenic gammadelta T cells with vaginal epithelial cell suspensions induced the vaginal gammadelta phenotype on the splenic gammadelta T cells. The finding of transgenic gammadelta T cells in the vaginal epithelium suggests that homing of gammadelta T cells to this site is not restricted to gammadelta T cells that express the V4/NS1 invariant TCR. Furthermore, these findings imply that retention of gammadelta T cells in the vaginal epithelium of normal mice is affected by a Vgamma4/Vdelta1-specific mechanism. The finding of a significant level of apoptosis in the transgenic vaginal gammadelta T cells, but not in the normal vaginal gammadelta T cells, could reflect that the mechanism of retention of Vgamma4/Vdelta1 + in the vaginal epithelium involves selective survival at the site.
Rakasz
E
E
Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
Rigby
S
S
de Andres
B
B
Mueller
A
A
Hagen
M
M
Dailey
M O
MO
Sandor
M
M
Lynch
R G
RG
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D018801:CD2 Antigens / Q000096:biosynthesis; D018106:CD28 Antigens / Q000096:biosynthesis; D002465:Cell Movement; D002478:Cells, Cultured; D004848:Epithelium; D005260:Female; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D019041:L-Selectin / Q000096:biosynthesis; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis*; D016201:Receptors, Lymphocyte Homing / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D019076:Transgenes; D014621:Vagina / Q000166:cytology* / Q000502:physiology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D018801:CD2 Antigens; D018106:CD28 Antigens; D018960:Hyaluronan Receptors; D019041:L-Selectin; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016201:Receptors, Lymphocyte Homing; D000099192:CD69 Antigens