MHC-linked colonization of the thymus and thymocyte development: effects of mature T lymphocytes

Abstract

Effects of mature T lymphocytes on thymic colonization by lymphohemopoietic cells were investigated in an in vitro experimental model, using a variety of experimental strategies. Lymphoid-depleted fetal thymus (FT) explants (C57BL/Ka, Thy1.1, H-2b) were incubated with bone marrow (BM) cells from syngeneic (C57BL/Ka; SBM) and allogeneic (BALB/c, Thy1.2, H-2d; ABM) donors. Cocultures of FT with SBM and ABM, depleted of Thy1+ or of CD3+ cells, resulted in equal proportions of lymphocytes from both BM donors. When peripheral blood lymphocytes (PBL) from synegenic or semi-allogeneic donors (F1[C57BL/Ka x C57BL/6J], Thy1.1/Thy1.2); or F1[C57BL/Ka x BALB/c], Thy1.1/Thy1.2, respectively) were added to these cultures, the total lymphocyte count per thymic lobe decreased and a developmental preference of the SBM-derived cells, as compared to the ABM-derived cells, was noted. Cells of the PBL types were also observed in the cultures. Cocultures of FT with ABM and PBL showed reduced proportions of ABM-derived cells and occurrence of cells of the PBL type. Finally, FT explants partially depleted of lymphocytes by irradiation (6 Gy), were cocultured with PBL from either syngeneic or allogeneic donors. In the presence of syngeneic PBL, the total number of cells and the proportion of double-positive (CD4+CD8+) T cells were similar to those in the FT cultured by itself, whereas in the presence of allogeneic PBL these values were reduced. The study suggests that mature T lymphocytes may play a role in the developmental processes in the thymus, and points to MHC-linked selective effects.