Interleukin-4 impairs granzyme-mediated cytotoxicity of Simian virus 40 large tumor antigen-specific CTL in BALB/c mice.
In this report we analyzed the impact of interleukin-4 (IL-4) on tumor-associated simian virus 40 (SV40) large T-antigen (TAg)-specific CD8+ cytotoxic T cells during rejection of syngeneic SV40 transformed mKSA tumor cells in BALB/c mice. Strikingly, challenge of naïve mice with low doses of mKSA tumor cells revealed a CD8+ T cell-dependent prolonged survival time of naïve IL-4-/- mice. In mice immunized with SV40 TAg we observed in IL-4-/- mice, or in wild type mice treated with neutralizing anti-IL-4 monoclonal antibody, a strongly enhanced TAg-specific cytotoxicity of tumor associated CD8+ T cells. The enhanced cytotoxicity in IL-4-/- mice was accompanied by a significant increase in the fraction of CD8+ tumor associated T-cells expressing the cytotoxic effector molecules granzyme A and B and in granzyme B-specific enzymatic activity. The data suggest that endogenous IL-4 can suppress the generation of CD8+ CTL expressing cytotoxic effector molecules especially when the antigen induces only a very weak CTL response.
Baschuk
Nikola
N
Institute for Medical Microbiology, Immunology und Hygiene, Medical Center of the University of Cologne, 50935, Cologne, Germany.
Utermöhlen
Olaf
O
Gugel
Roland
R
Warnecke
Gabriele
G
Karow
Ulrike
U
Paulsen
Daniela
D
Brombacher
Frank
F
Krönke
Martin
M
Deppert
Wolfgang
W
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology*; D000957:Antigens, Viral, Tumor / Q000276:immunology*; D002461:Cell Line, Transformed; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D053804:Granzymes / Q000378:metabolism*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009369:Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor; D015847:Interleukin-4; D053804:Granzymes