Effect of mouse thymic medullary epithelial cell line on thymocyte development and functional maturationin vivo

Thymic medullary type epithelial cell line (MTEC1), which expressed H-2D(d) and Ia(d), was derived from BALB/c mouse. MTEC1 cells were introduced by intrathymic injection into irradiated H-2(b) mice reconstituted with H-2(bxd) F1bone marrow cells. Two months later, the injected MTEC1 cells were found to be still present in the recipient thymus. Splenocytes from chimeric mice, inin vitro functional assays, were analyzed to investigate whether the MTEC1 cellsin vivo could induce the production of H-2(d) restricted antigen-specific T cells. The H-2(d) restricted VSV-antigen specific proliferating and IL-2 producing T cells as well as H-2(d) restricted influenza virus specific cytotoxic T cells were found in chimeric mice injected with MTEC1 cells, and these cells were shown to be tolerant to H-2(d) selfantigen. On the contrary, H-2(d) restricted antigen-specific and H-2(d) self-antigen tolerant T cells were not shown in control mice injected with saline. These results suggest that intrathymically injected MTEC1 cells could induce T lineage cell development and functional maturation in the intact thymus. A hypothesis of "second thymic selection" in thymic medulla has been postulated and its implication discussed.