Type 1 and type 2 CD8+ effector T cell subpopulations promote long-term tumor immunity and protection to progressively growing tumor.
Cytolytic CD8+ effector cells fall into two subpopulations based on cytokine secretion. Type 1 CD8+ T cells (Tc1) secrete IFN-gamma, whereas type 2 CD8+ T cells (Tc2) secrete IL-4, IL-5, and IL-10. Using an OVA-transfected B16 lung metastases model, we assessed the therapeutic effects of adoptively transferred OVA-specific Tc1 and Tc2 subpopulations in mice bearing established pulmonary malignancy. Effector cell-treated mice exhibiting high (5 x 105) tumor burdens experienced significant (p < 0.05) delays in mortality compared with those of untreated control mice, whereas high proportions (70-90%) of mice receiving therapy with low (1 x 105) tumor burdens survived indefinitely. Long-term tumor immunity was evident by resistance to lethal tumor rechallenge, heightened levels of systemic OVA Ag-specific CTL responses ex vivo, and detection of long-lived TCR transgene-positive donor cells accompanied by an elevation in the total numbers of CD8+ CD44high activated and/or memory T cells at sites of tumor growth. Long-lasting protection by Tc2 and Tc1 effector cells were dependent, in part, on both the level of tumor burden and effector cell-derived IL-4, IL-5, and IFN-gamma, respectively. We conclude that Tc1 and Tc2 effector cells provide immunity by different mechanisms that subsequently potentiate host-derived antitumor responses.
Dobrzanski
M J
MJ
Trudeau Institute, Saranac Lake, NY 12983, USA.
Reome
J B
JB
Dutton
R W
RW
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D010047:Ovalbumin / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D013997:Time Factors
D018984:Epitopes, T-Lymphocyte; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin