Tripartite motif-containing protein 30 modulates TCR-activated proliferation and effector functions in CD4⁺ T cells

To avoid excessive activation, immune signals are tightly controlled by diverse inhibitory proteins. TRIM30, a tripartite motif (TRIM)-containing protein is one of such inhibitors known to function in macrophages. To define the roles of TRIM30, we generated Trim30 knockout (Trim30^-/-) mice. Trim30 deletion caused no major developmental defects in any organs, nor showed any discernable defect in the activation of macrophages. But, Trim30 ^-/- mice showed increased CD4/CD8 ratio when aged and Trim30 ^-/- CD4⁺ T cells exhibited an abnormal response upon TCR activation, in particular in the absence of a costimulatory signal. Adoptive transfer of wild-type and Trim302/2 CD4+ T cells together into lymphopenic hosts confirmed higher proliferation of the Trim30^-/- CD4⁺ T cells in vivo. Despite the enhanced proliferation, Trim30^-/- T cells showed decreased levels of NF-κB activation and IL-2 production compared to wild-type cells. These results indicate a distinct requirement for TRIM30 in modulation of NF-κB activation and cell proliferation induced by TCR stimulation.