Thymic shared antigen-2: A novel cell surface marker associated with T cell differentiation and activation

Thymic shared Ag-2 (TSA-2) is a 28-kDa, glycophosphatidylinitosol- linked cell surface molecule expressed on various T cell and thymic stromal cell subsets. It is expressed on most CD3^-CD4^-CD8^-, CD4⁺CD8⁺, and CD3(high)CD4^-CD8⁺ thymocytes but is down-regulated on ≃40% of CD3(high)CD4⁺CD8^- thymocytes. Expression on peripheral TCR. αβ⁺ T cells is similar to that of CD3⁺ thymocytes, although a transient down-regulation occurs with cell activation. Consistent with the recent hypothesis that emigration from the thymus is an active process, recent thymic emigrants are primarily TSA-2(-/low). TSA-2 expression reveals heterogeneity among subpopulations of CD3(high)CD4⁺CD8^- thymocytes and TCR-γδ⁺ T cell previously regarded as homogenous. The functional importance of TSA-2 was illustrated by the severe block in T cell differentiation caused by adding purified anti-TSA-2 mAb to reconstituted fetal thymic organ culture. While each CD25/CD44-defined triple-negative subset was present, differentiation beyond the TN stage was essentially absent, and cell numbers of all subsets were significantly below those of control cultures. Cross-linking TSA-2 on thymocytes caused a significant Ca²⁺ influx but no increase in apoptosis, unless anti-TSA-2 was used in conjunction with suboptimal anti-CD3 mAb. Similar treatment of mature TSA-2⁺ T cells had no effect on cell survival or proliferation. This study reveals TSA-2 to be a functionally important molecule in T cell development and a novel indicator of heterogeneity among a variety of developing and mature T cell populations.