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

Journal Article · Wed Oct 01 04:00:00 EDT 2014 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2014.07.028· OSTI ID:22416932

Ryu, Min Sook ^[1]; Woo, Min-Yeong ^[2]; Kwon, Daeho ^[3]; Hong, Allen E. ^[1]; Song, Kye Yong ^[4]; Park, Sun ^[2]; Lim, In Kyoung ^[1]

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1. Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of)
2. Department of Microbiology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of)
3. Department of Microbiology, Kwandong University College of Medicine, Gangneung, Gangwon-do 210-701 (Korea, Republic of)
4. Department of Pathology, Chung-Ang University College of Medicine, Dongjak-gu, Seoul 156-756 (Korea, Republic of)

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) mice. Proliferation and survival of mature T cells were significantly increased in the KO than the wild type (WT) 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{sup +} 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{sup +} CD8{sup +} 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{sup +} CD8{sup +} T cells in the splenocytes of KO mice may affect the loss of CD8{sup +} 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{sup +} CD8{sup +} T-cells and CD107a{sup +} CD8{sup +} T-cells, thus transiently regulating in vivo anti-tumor immunity. - Highlights: • 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{sup +} T cell infiltration in tumor. • Reduction of CD 107{sup +}CD8{sup +} T cells, but increased granzyme B{sup +} CD8{sup +} T cells in TIS21KO mice.

• OSTI ID: 22416932
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 327; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL PROLIFERATION
GENES
IN VITRO
IN VIVO
MELANOMAS
MICE
RECEPTORS
SPLEEN
TUMOR CELLS