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Expression and function of a 90-kilodalton homodimeric molecule (10D1 antigen) on human thymocytes
T Kobata1, H Yagita, H Matsuda
1Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Insights
The 10D1 antigen (Ag) is found on specific human T cells and thymocytes. Its functional expression, particularly in inducing proliferation, is primarily on mature CD4+ thymocytes via the IL-2/IL-2 receptor system.
Area of Science:
- Immunology
- Cell Biology
- T cell development
Background:
- The 10D1 antigen (Ag) is a 90-kDa homodimeric molecule implicated in T cell activation.
- Its expression and function on human thymocytes, crucial for T cell development, remain incompletely understood.
Purpose of the Study:
- To investigate the expression pattern of the 10D1 Ag on human thymocytes.
- To elucidate the functional role of the 10D1 Ag in thymocyte activation and proliferation.
Main Methods:
- Three-color flow cytometry (FMF) was employed to analyze 10D1 Ag expression on thymocyte subpopulations.
- Monoclonal antibodies (mAbs) against 10D1 Ag, T cell markers (CD4, CD8, CD7, CD2, CD3), and the IL-2/IL-2 receptor (IL-2R) system were used.
- Proliferation assays were conducted on thymocytes stimulated with 10D1 mAb.
Main Results:
- 10D1 Ag was highly expressed on distinct subpopulations of double-negative and CD4 single-positive thymocytes, weakly on double-positive, and absent on CD8 single-positive thymocytes.
- In double-negative thymocytes, 10D1+ cells were predominantly immature (CD7+2+3-).
- 10D1 mAb induced proliferation of CD4+8- thymocytes, dependent on the IL-2/IL-2R system, with proliferating cells expressing IL-2R alpha (p55).
Conclusions:
- Functional expression of 10D1 Ag is restricted to a minor, more mature CD4+ thymocyte population, similar to peripheral blood T cells.
- The 10D1 Ag plays a role in T cell activation pathways, particularly in CD4+ thymocytes through the IL-2/IL-2R system.
- These findings contribute to understanding alternative T cell activation pathways and thymocyte maturation.
Abstract:
The 10D1 Ag is a 90-kDa homodimeric molecule specifically expressed on a subpopulation of human T cells, and is involved in an alternative pathway of T cell activation. In the present study, we have examined the expression and function of the 10D1 Ag on human thymocytes. Three-color FMF analysis showed that the 10D1 Ag was highly expressed on minor but distinct subpopulations of double-negative and CD4 single-positive thymocytes, and weakly on a part of double-positive thymocytes, but not on CD8 single-positive thymocytes. In double-negative thymocytes, the vast majority of 10D1+ cells were immature thymocytes of CD7+2+3- phenotype. Interestingly, 10D1 mAb could induce the proliferation of CD4 single-positive thymocytes in the presence of goat anti-mouse Ig to cross-link the 10D1 Ag. The treatment of thymocytes with OKT4 mAb plus C but not with OKT8 mAb plus C totally abrogated the proliferative response induced by 10D1 mAb, indicating that the 10D1-responsible thymocytes were of CD4+8- phenotype. This 10D1 mAb-induced thymocyte proliferation was perfectly dependent on the endogenous IL-2/IL-2R system since a complete inhibition was observed with anti-IL-2 and anti-IL-2R mAb. The proliferating CD4 single positive thymocytes predominantly expressed the IL-2R alpha (p55) but not a detectable level of the IL-2R beta (p75). These results indicate that, although the 10D1 Ag can be detected on the CD7+2+3-4-8- thymocytes, its functional expression is restricted to a minor more mature CD4+ thymocyte population as well as in peripheral blood T cells, and the implications of these findings are discussed.