Tumor and CD4 T-cell interactions: tumor escape as result of reciprocal inactivation.
This paper addresses the capacity of naive, effector, and memory CD4 T cells to control growth of a major histocompatibility complex (MHC) class II-positive B-cell lymphoma in vivo. To assess the role of T cells on their own without contributions by B cells, antibodies, or natural killer (NK) cells, we generated pure effector or memory CD4 T cells in Rag-/-gc-/- mice deficient in endogenous lymphocytes and NK cells. Lymphoma cells expressing a model antigen were injected into mice with T cells of cognate specificity that were either naive or in effector or resting memory state. Naive T cells were unable to prevent tumor growth, probably due to delay of efficient cross-presentation by dendritic cells. However, both effector and memory T cells, dependent on the amount of antigen available, controlled the tumor for a considerable period of time without the need for dendritic cell stimulation. Nevertheless, the tumor eventually grew uncontrolled in all cases. This was not because of a defect in T-cell homing to the tumor site or loss of MHC class II or costimulatory molecules by the tumor, but reflected mutual paralysis of T-cell responsiveness and antigen processing by tumor cells.
Flynn
Sarah
S
Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, Mill Hill, London United Kingdom. bstocki@nimr.mrc.ac.uk
Stockinger
Brigitta
B
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003182:Complement C5 / Q000276:immunology; D000949:Histocompatibility Antigens Class II; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology
D003182:Complement C5; D000949:Histocompatibility Antigens Class II