The role of NKT cells on antitumor activity of CpG oligodeoxynucleotides (ODNs) was evaluated by peritumoral injections of CpG-ODNs in s.c. melanoma-bearing mice of strains differing in the number of NKT cells (athymic nude mice, recombination-activating gene-/-/transgenic Vα14/Vβ8.2 mice that generate NKT cells; Jα281-/- mice and CD1-/- mice, which both have a strongly reduced number of NKT cells; and C57BL/6 wild-type mice). Tumor growth was significantly inhibited in strains enriched or depleted of NKT cells. The two murine strains having a reduced number of NKT cells differed significantly in the CpG-dependent tumor growth inhibition: in Jα281-/- mice this inhibition was superimposable to that observed in C57BL/6 mice, while in CD1-/- mice the inhibition was dramatic. The increased tumor inhibition in CD1-/- correlated with a significantly higher ratio of IFN-γ-IL-4 production in response to CpG as compared with C57BL/6 and Jα281-/- mice. Experiments in which preparations of APCs and lymphocytes of the three strains were mixed showed that in the presence of APCs not expressing CD1, the production of CpG-ODN-induced type 1 cytokines was higher. Phenotype analysis of IFN-γ- and IL-4-producing cells revealed that the differences between CD1-/- and C57BL/6 in the production of these two cytokines were mainly due to CD3+ T lymphocytes. These data point to a regulatory role for the CD1 molecule in antitumor activity induced by danger signals, independently of Vα14 NKT cells. The identification of a CD1-dependent suppressive subpopulation(s) might have important implications for the study of tolerance in the context of cancer, autoimmunity, and transplantation.

Absence of the CD1 molecule up-regulates antitumor activity induced by CpG oligodeoxynucleotides in mice / L. Sfondrini, D. Besusso, M.T. Zoia, M. Rodolfo, A.M. Invernizzi, M. Taniguchi, T. Nakayama, M.P. Colombo, S. Mènard, A. Balsari. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 169:1(2002 Jul 01), pp. 151-158.

Absence of the CD1 molecule up-regulates antitumor activity induced by CpG oligodeoxynucleotides in mice

L. Sfondrini
Primo
;
D. Besusso
Secondo
;
A. Balsari
Ultimo
2002-07-01

Abstract

The role of NKT cells on antitumor activity of CpG oligodeoxynucleotides (ODNs) was evaluated by peritumoral injections of CpG-ODNs in s.c. melanoma-bearing mice of strains differing in the number of NKT cells (athymic nude mice, recombination-activating gene-/-/transgenic Vα14/Vβ8.2 mice that generate NKT cells; Jα281-/- mice and CD1-/- mice, which both have a strongly reduced number of NKT cells; and C57BL/6 wild-type mice). Tumor growth was significantly inhibited in strains enriched or depleted of NKT cells. The two murine strains having a reduced number of NKT cells differed significantly in the CpG-dependent tumor growth inhibition: in Jα281-/- mice this inhibition was superimposable to that observed in C57BL/6 mice, while in CD1-/- mice the inhibition was dramatic. The increased tumor inhibition in CD1-/- correlated with a significantly higher ratio of IFN-γ-IL-4 production in response to CpG as compared with C57BL/6 and Jα281-/- mice. Experiments in which preparations of APCs and lymphocytes of the three strains were mixed showed that in the presence of APCs not expressing CD1, the production of CpG-ODN-induced type 1 cytokines was higher. Phenotype analysis of IFN-γ- and IL-4-producing cells revealed that the differences between CD1-/- and C57BL/6 in the production of these two cytokines were mainly due to CD3+ T lymphocytes. These data point to a regulatory role for the CD1 molecule in antitumor activity induced by danger signals, independently of Vα14 NKT cells. The identification of a CD1-dependent suppressive subpopulation(s) might have important implications for the study of tolerance in the context of cancer, autoimmunity, and transplantation.
Settore MED/04 - Patologia Generale
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/174920
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