Committed memory effector type 2 cytotoxic T (Tc2) cells are ineffective in protective anti-tumor immunity.
Cytotoxic CD8+ T cells (Tc) are a major effector cell population in protection against tumor growth and classified into Tc1 or Tc2 based on their cytokine-secreting profiles. However, their relative tumor protective roles remain undefined. In the present study, CD8+ memory T cells were obtained from mice given with CT26-IL 12 and tumor-specific Tc1 and Tc2 cells were induced by in vitro primary stimulation (1 degrees). In vivo anti-tumor immunity and in vitro cytotoxicity of 1 degrees Tc2 memory effector cells were highly protective comparably to 1 degrees Tc1, but they secreted high level of IFNgamma as well as IL 4 and IL 5. Moreover, memory cells obtained again from tumor-protected mice by either 1 degrees Tc1 or Tc2 transfer showed indistinguishable, Tc1-like, cytokine profiles. These results strongly suggest that 1 degrees Tc2 cells are insufficiently polarized. Tc2 memory effector cells were therefore examined for their transitional anti-tumor activity during consecutive stimulation until Th2 commitment. Secondary stimulation (2 degrees) markedly reduced secretion of IFNgamma (by 94%) and in vivo tumor protection (by 83%). Tertiary (3 degrees) and further stimulation completely abrogated both of tumor protective activity and IFNgamma secretion of Tc2 cells. This progressive loss of activity following repeated stimulation was accompanied by a reduction of in vitro cytotoxicity to CT26 tumor cells. In addition, when 1 degrees Tc2 cells were trans-differentiated to Tc1 during secondary stimulation, 2 of 6 cultures recovered tumor protective activity concomitantly with IFNgamma secretion, indicating that repeated stimulation does not deteriorate tumor protective activity of 2 degrees Tc2 cells. Collectively, these data demonstrate that highly committed Tc2 cells are ineffective in tumor protection.
Department of Biological Science, School of Science and Technology, Jeonju University, Jeonju 560-759, South Korea.
Jeong-Su
JS
Do
Youn-Hwa
YH
Choi
Sung-Hye
SH
Shin
Ho Keun
HK
Yi
Pyung Han
PH
Hwang
Sang-Yun
SY
Nam
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D007111:Immunity, Cellular; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016207:Cytokines