Induction of terminal deoxynucleotidyl transferase and Lyt antigens with thymosin: identification of multiple subsets of prothymocytes in mouse bone marrow and spleen.

Thymosin (fraction 5 and synthetic alpha 1 peptide) induced prothymocytes in mouse bone marrow and spleen to express terminal deoxynucleotidyl transferase (TdT; DNA nucleotidylexotransferase; nucleosidetriphosphate:DNA deoxynucleotidylexotransferase, EC 2.7.7.31) or Lyt-1+, 2+, 3+ alloantigens (or both) after brief incubation in vitro. Three antigenic phenotypes were generated: (i) TdT+ Lyt+, (ii) TdT- Lyt+, and (iii) TdT+ Lyt-. The TdT+ Lyt+ phenotype was expressed by 80% of prothymocytes in bone marrow and 30% of prothymocytes in spleen from normal mice. The TdT- Lyt+ phenotype was expressed by 81% of prothymocytes in bone marrow from athymic mice. More than 80% of TdT+ bone marrow cells from normal and athymic mice expressed Lyt antigens after thymosin treatment. We interpret these observations as suggesting that (i) most TdT+ hemopoietic cells in normal and athymic mice are thymocyte progenitors; (ii) two independent lineages of prothymocytes exist, one that expresses TdT and another that does not, (iii) commitment of prothymocytes to the TdT+ cell pathway is partially regulated by a thymic feedback mechanism; and (iv) the bone marrow preferentially produces TdT+ prothymocytes, whereas the spleen may serve as a repository for TdT- prothymocytes. A model of T-cell development is presented in which the thymus functions as a compound organ to process TdT+ and TdT- thymocytes progenitors and to generate two lines of T cells.