T-cell subset analysis of Lewis lung carcinoma tumor rejection: heterogeneity of effectors and evidence for negative regulatory lymphocytes correlating with metastasis.
We have analyzed the phenotypes of the T-cell subsets generated in response to Lewis lung carcinoma clones in C57BL/6J recipients. The metastatic derivative, which expresses low levels of H-2Kb gene, predominantly elicited CD8, V beta 8, and V beta 9+ T-cells. The nonmetastatic clone expressing high levels of H-Kb gene triggered a more heterogeneous response of V beta-5, -6, -8, -9, and -11 CD8+ T-cells. Comparison of the T-cell receptor (TCR) expression of the T-cells infiltrating the tumor site with the lymphocytes in the periphery of tumor-bearing animals revealed a pattern of homing of CD4+ T-cells bearing V beta-5, -6, and -11 TCR chains and CD8+ T-cells bearing V beta-5, -6, -9, and -11. Depletion of V beta 5 or V beta 6+ T-cells correlated with accelerated tumor growth, implying their protective role as tumor-specific effectors and consistent with the cytotoxicity of T-cells with this TCR phenotype. V beta 11 TCR expression in the tumor-infiltrating lymphocytes increased with the tumor size. Depletion of V beta 11+ T-cells enhanced resistance to primary tumor growth and conferred protection from metastasis in recipients cleared of V beta 5 and V beta 6 T-cell subsets. Those results suggest that tumor-specific effectors as well as negative regulator T-cells home, infiltrate, and coexist in the tumor site.
Gelber
C
C
Division of Immunology and Rheumatology, Stanford University School of Medicine, California 94305.
Eisenbach
L
L
Feldman
M
M
Goodenow
R S
RS
D000818:Animals; D016525:Antigenic Modulation; D016516:CD4-CD8 Ratio; D016827:CD8 Antigens / Q000276:immunology; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology / Q000556:secondary; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D007111:Immunity, Cellular; D016867:Immunocompromised Host; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D007959:Lymphocyte Culture Test, Mixed; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell