T cells developing in fetal thymus of T-cell receptor alpha-chain transgenic mice colonize gammadelta T-cell-specific epithelial niches but lack long-term reconstituting potential.
The gammadelta T cells generated during mouse fetal development are absolutely dependent on their invariant T-cell receptors (TCRs) for their function. However, there is little information on whether the epithelial homing properties of fetal T cells might also be developmentally induced by factors unrelated to TCR specificity. We have previously described TCR alpha-chain transgenic (2B4 TCR-alpha TG) mice, in which the transgenic TCR alpha-chain is expressed early, already at embryonic day 14 (E14). These mice have a large population of 'gammadelta T-cell-like' CD4- CD8- (double-negative; DN) alphabeta T cells, some of which develop during E14-E18 contemporarily to intraepithelial lymphocytes (IELs) expressing invariant TCR-gammadelta. Using the 2B4 TCR-alpha TG mouse model we have been able to more precisely study the impact of a variant TCR expression on IEL development and homing. In this study we show that TCR-alpha TG and TCR-alpha TG crossed to TCR-delta-deficient mice (TCR-alpha TG x TCR-delta-/-) carry TG TCR-alpha+ dendritic epidermal T cells (DETCs) and TCR-alpha TG+ IELs in the small intestine. The TG+ DETCs develop and seed the epidermis with similar kinetics as Vgamma5+ DETCs of normal mice, in contrast to the TCR-alphabeta+ DETCs found in TCR-delta-/- mice. However, whereas the intestinal TCR-alpha TG+ IELs persist in old mice (> 20 months), the TCR-alpha TG+ DETCs do not. The data in this study indicate that the timing of TCR expression and thereby development during ontogeny regulates the specific homing potential for fetal T cells but not their subsequent functions and properties.
Leandersson
Karin
K
Experimental Pathology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, Sweden. karin.leandersson@med.lu.se
Jaensson
Elin
E
Ivars
Fredrik
F
D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement; D049109:Cell Proliferation; D004817:Epidermis / Q000276:immunology; D005434:Flow Cytometry; D005865:Gestational Age; D007413:Intestinal Mucosa / Q000196:embryology / Q000276:immunology*; D007421:Intestine, Small / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D013950:Thymus Gland / Q000196:embryology* / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta