In vitro analysis of thymic microenvironmental effects on bone marrow cells of severe combined immunodeficient (SCID) mice.

The effect of the thymic microenvironment on thymocyte development from lymphohemopoietic cells was studied in an in vitro experimental model. Fetal thymus explants (FT, 15 days of gestation, C57BL/Ka, Thy1.1) were cocultured with bone marrow (BM) cells of severe combined immunodeficient (SCID, C.B.-17 scid/scid) or of normal BALB/c mice. The FT explants were depleted of their own lymphocytes either by irradiation (10 or 20 Gy) or by 2-deoxyguanosine (dGua) treatment. Development of SCID BM-derived Thy1+ cells was observed in coculture with the severely lymphocyte-depleted FT explants (dGua, 20 Gy), whereas BALB/c BM-type T cells were also apparent in the mildly irradiated (10 Gy) FT. The SCID BM-derived thymocytes were characterized as CD3- subpopulations expressing CD4/CD8 markers, while CD3+ CD4/CD8 subsets developed from the BALB/c mice. In contrast to results on BM-derived cells, cocultures of FT with thymus cells from SCID mice yielded CD3- CD4- CD8- Thy1.2+ cells, as opposed to BALB/c-derived Thy1.2+CD3+ cells exhibiting different CD4/CD8 phenotypes. Our data indicate that the BM cells from SCID mice can be induced to limited differentiation within the thymic microenvironment and this seems to be inhibited in the presence of resident radioresistant thymic cells.