FUNCTIONAL CHARACTERIZATION OF PRETHYMIC T CELLS COMMITTED TO ALLOREACTIVITY

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Abstract
The results of previous experiments on MHC fully allogeneic bone marrow transplantation (BMT) in nonthymectomizd recipients indicated that anti-MHC alloreactivity starts to become irreversibly committed at the prethymic level. This is a matter of some controversy. Since it is possible that conflicting results depend on the methods chosen, we reexamined our previous results by applying two new approaches. Adult thymectomized (ATX) Balb/c mice received a syngeneic fetal thymus either 3 weeks before or 3 weeks after lethal irradiation and reconstitution with C57BL/6 BM incubated in antiserum. Since monoclonal antibodies such as anti-Thy 1 are of limited value for investigations of the above type (Thy 1 antigen crosses the prethymic/thymic border), we used two highly selective, excessively cytotoxic xenoantisera for incubation of the donor BM—either a specific anti-T cell serum (SAT) that eliminated only mature T cells, or a specific antilymphocyte serum (SAL) that reacted additionally with a subset of prethymic T cells (PTC). In both experimental approaches the results were similar: (1) Recipients of SAT-BM developed antihost reactivity, in contrast to recipients of SAL-BM. (2) SAT-BM recipients became immunodeficient, whereas SAL-BM chimeras were immunocompetent. (3) Late mortality was observed only following SAT treatment. (4) Preliminary morphological findings in the lymphoid tissue of BM recipients agree fully with the functional observations. We conclude that the data confirm our previous results in nonthymectomized BM recipients—i.e., PTCs initiate antihost reactivity in MHC fully allogeneic BMT—and PTC commitment is thymus/thymus factor independent. These conclusions are discussed with regard to the problems of MHC allogeneic clinical BMT.