Effect of Med1 on T cell development and CD4(+) T cell differentiation in immune response.

OBJECTIVES: The differentiation of CD4(+) T cells is regulated by a complex and fine signaling pathway composed of many molecules during immune response, and the molecular mechanism for regulating T-bet expression is unclear. Mediator complex subunit 1 (Med1) can combine with a variety of co-factors to regulate gene transcription, promote cell proliferation and survival, and affect invariant natural killer T cell (iNKT) development. This study aims to investigate the effect of Med1 on T cell development and CD4(+) T cell differentiation in immune response. METHODS: Mice with T cell-specific knockout of Med1 gene (Med1(F/F)CD4cre(+), KO) were constructed and verified. The percentage and number of CD4(+) and CD8(+) T cells in thymus, spleen, and lymph nodes of KO mice and control (Con) mice (Med1(F/F)CD4cre(-)) were detected by flow cytometry. After 8 days of infection with lymphocytic choriomeningitis virus (LCMV), the percentage and number of CD4(+) T cells or antigen-specific (GP66(+)) CD4(+) T cells, the percentage and number of Th1 cells (Ly6c(+)PSGL1(+)) in CD4(+) T cells or antigen-specific CD4(+) T cells were examined in the spleen of mice. Moreover, the fluorescence intensity of T-bet in CD4(+) T cells or antigen-specific CD4(+) T cells was analyzed. RESULTS: Compared with the Con group, the percentage and number of CD4(+) T cells and CD8(+) T cells in the thymus, CD4(+) T cells in the spleen and lymph nodes of the KO group showed no significant differences (all P>0.05), but the percentage and number of CD8(+) T cells in the spleen and lymph nodes of the KO group were diminished significantly (all P<0.05). After 8 days of infection with LCMV, there was no significant difference in the percentage and number of CD4(+) T cells or antigen-specific CD4(+) T cells in the spleen between the KO group and the Con group (all P>0.05), while in comparison with the Con group, the percentage and number of Th1 cells in CD4(+) T cells or antigen-specific CD4(+) T cells, and the expression of T-bet in CD4(+) T cells or antigen-specific CD4(+) T cells were significantly reduced in the spleen of the KO group (all P<0.05). CONCLUSIONS: Specific knockout of Med1 in T cells does not affect the development of CD4(+) and CD8(+) T cells in the thymus, but does affect the maintenance of peripheral CD8(+) T cells. In the immune response, Med1 gene deletion affects the expression of transcription factor T-bet, which in turn to reduce Th1 cell differentiation.