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 gene (Med1CD4cre, 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 (Med1CD4cre) 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 (Ly6cPSGL1) 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 >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 <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 >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 <0.05).

Conclusions: Specific knockout of 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, gene deletion affects the expression of transcription factor T-bet, which in turn to reduce Th1 cell differentiation.