Committed memory effector type 2 cytotoxic T (Tc2) cells are ineffective in protective anti-tumor immunity
| Autor: | Sang-Yun Nam, Sung-Hye Shin, Pyung Han Hwang, Youn-Hwa Choi, Ho Keun Yi, Jeong-Su Do |
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| Rok vydání: | 2004 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cytotoxicity Immunologic Male medicine.medical_treatment Immunology Stimulation Biology Mice T-Lymphocyte Subsets Cell Line Tumor medicine Immunology and Allergy Cytotoxic T cell Animals IL-2 receptor Interleukin 4 Immunity Cellular Mice Inbred BALB C Lymphokine-activated killer cell Neoplasms Experimental Cell biology Cytokine Colonic Neoplasms Interleukin 12 Cytokines Immunologic Memory CD8 Neoplasm Transplantation T-Lymphocytes Cytotoxic |
| Zdroj: | Immunology letters. 95(1) |
| ISSN: | 0165-2478 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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