Accumulation of cytolytic CD8+ T cells in B16-melanoma and proliferation of mature T cells in TIS21-knockout mice after T cell receptor stimulation

• Constitutive expression of TIS21 in splenocytes and upregulation by TCR stimulation.
• Proliferation of mature T-cells in spleen of TIS21KO mice after TCR stimulation.
• Inhibition of cell death in mature T-cells of TIS21KO mice compared with the wild type.
• Inhibition of melanoma growth in TIS21KO mice and CD8+ T cell infiltration in tumor.
• Reduction of CD 107+CD8+ T cells, but increased granzyme B+ CD8+ T cells in TIS21KO mice.

In vivo and in vitro effects of TIS21 gene on the mature T cell activation and antitumor activities were explored by employing MO5 melanoma orthograft and splenocytes isolated from the TIS21-knockout (KO) 2 mice. Proliferation and survival of mature T cells were significantly increased in the KO than the wild type (WT)3 cells, indicating that TIS21 inhibits the rate of mature T cell proliferation and its survival. In MO5 melanoma orthograft model, the KO mice recruited much more CD8+ T cells into the tumors at around day 14 after tumor cell injection along with reduced tumor volumes compared with the WT. The increased frequency of granzyme B+ CD8+ T cells in splenocytes of the KO mice compared with the WT may account for antitumor-immunity of TIS21 gene in the melanoma orthograft. In contrast, reduced frequencies of CD107a+ CD8+ T cells in the splenocytes of KO mice may affect the loss of CD8+ T cell infiltration in the orthograft at around day 19. These results indicate that TIS21 exhibits antiproliferative and proapoptotic effects in mature T cells, and differentially affects the frequencies of granzyme B+ CD8+ T-cells and CD107a+ CD8+ T-cells, thus transiently regulating in vivo anti-tumor immunity.