Med1对T细胞发育及CD4⁺ T细胞在免疫应答中分化的影响

Objective: 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/FCD4cre⁺ , 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/FCD4cre⁻) 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). Conclusion: 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.