Maturation of medullary thymic epithelium requires thymocytes expressing fully assembled CD3-TCR complexes.

Unlike medullary thymic epithelial cells (TEC) of normal mice, medullary TEC of TCR- SCID mice are immature and disorganized. In order to assess directly the role of TCR+ cells in the development of medullary TEC, we bred mice which co-expressed the SCID genetic defect and transgenes encoding clonotypic TCR chains. Immunohistologic examination revealed that medullary thymic epithelial cells from TCR beta transgenic SCID mice, whose thymocytes only express TCR beta chains that inefficiently associate with CD3 and zeta components, remained immature and disorganized. In contrast, medullary TEC from TCR alpha beta transgenic SCID mice, whose thymocytes express fully assembled CD3-zeta-TCR alpha beta complexes were mature and organized. Interestingly, the ability of TCR alpha beta(+)-zeta(+)-CD3+ thymocytes to induce maturation of medullary TEC appeared not to be related to the antigen specificity of the TCR as thymi from positively selecting, negatively selecting and non-selecting TCR alpha beta transgenic SCID mice all possessed induced medullary thymic epithelial cells. In addition, we found that induction of medullary TEC cells was associated with the presence of medullary thymocytes, including those of the CD4-CD8- TCR alpha beta+ phenotype. The present findings demonstrate that fully assembled CD3-zeta-TCR complexes are required to induce maturation of medullary thymic epithelial cells and indicate that thymocyte induction of medullary thymic epithelial cells may result from signaling independently of their clonotypic TCR chains.