Generation of tumor-associated cytotoxic T lymphocytes requires interleukin 4 from CD8(+) T cells.
Activation of tumor-associated CD8(+) cytotoxic T lymphocytes (CTLs) often requires antigen representation, e.g., by dendritic cells (DCs), and CD4(+) T cell help. Previously, we showed that CTL-mediated tumor immunity required interleukin 4 (IL-4) during the immunization but not effector phase. To determine the source and target cells of IL-4, we performed adoptive T cell transfers using CD4(+) and CD8(+) T cells from IL-4(-/-) and IL-4R(-/-) mice and analyzed CTL generation. Even though necessary for CTL generation, CD4(+) T cells did not need to express IL-4 or IL-4R. Surprisingly, CTL generation required IL-4 but not IL-4R expression by CD8(+) T cells. As IL-4 (a) was expressed by naive CD8(+) T cells within 24 h after antigen encounter, (b) IL-4 induced DC maturation, and (c) CTL development was impaired in T cell-reconstituted IL-4R(-/-) mice, CD8(+) T cell-derived IL-4 appears to act on DCs. We conclude that CD4(+) and CD8(+) T cells provide different signals for DC activation during CTL generation.
Schüler
T
T
Max-Delbrück-Center for Molecular Medicine, 13092 Berlin, Germany. tschue@mdc-berlin.de
Kammertoens
T
T
Preiss
S
S
Debs
P
P
Noben-Trauth
N
N
Blankenstein
T
T
D019264:Adoptive Transfer; D000818:Animals; D016827:CD8 Antigens / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D015847:Interleukin-4 / Q000276:immunology*; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D019948:Receptors, Interleukin-4 / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016827:CD8 Antigens; D019948:Receptors, Interleukin-4; D015847:Interleukin-4