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 ce ll surface molecule expressed on various T cell and thymic stromal cell sub sets. It is expressed on most CD3(-)CD4(-)CD8(-), CD4(+)CD8(+), and CD3(hig h)CD4(-)CD8(+) thymocytes but is down-regulated on similar to 40% of CD3(hi gh)CD4(+)CD8(-) thymocytes, Expression on peripheral TCR-alpha beta(+) T ce lls is similar to that of CD3(+) thymocytes, although a transient down-regu lation occurs with cell activation. Consistent with the recent hypothesis t hat emigration from the thymus is an active process, recent thymic emigrant s are primarily TSA-2(-/low). TSA-2 expression reveals heterogeneity among subpopulations of CD3(high)CD4(+)CD8(-) thymocytes and TCR-gamma delta(+) T cell previously regarded as homogenous, The functional importance of TSA-2 was illustrated by the severe block in T cell differentiation caused by ad ding purified anti-TSA-2 mAb to reconstituted fetal thymic organ culture. W hile each CD25/CD44-defined triple-negative subset was present, differentia tion beyond the TN stage was essentially absent, and cell numbers of all su bsets were significantly below those of control cultures. Cross-linking TSA -2 on thymocytes caused a significant Ca2+ influx but no increase in apopto sis, 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 surviv al or proliferation. This study reveals TSA-2 to be a functionally importan t molecule in T cell development and a novel indicator of heterogeneity amo ng a variety of developing and mature T cell populations.