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 CD3highCD4-CD8+ thymocytes but is down-regulated on approximately 40% of CD3highCD4+CD8- thymocytes. Expression on peripheral TCR-alphabeta+ 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 CD3highCD4+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 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.
Berzins
S P
SP
Department of Pathology and Immunology, Monash Medical School, Prahran, Australia. Stuart.Berzins@med.monash.edu.au
Davey
G M
GM
Randle-Barrett
E S
ES
Malin
M A
MA
Classon
B J
BJ
Fraser
S
S
Boyd
R L
RL
D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D015415:Biomarkers / Q000737:chemistry; D017252:CD3 Complex / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D004357:Drug Synergism; D005333:Fetus; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D009924:Organ Culture Techniques; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D017252:CD3 Complex; D008565:Membrane Proteins; C084839:thymic shared antigen-1; C118891:thymic shared antigen-2; D002118:Calcium