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

Lucia Sfondrini, Dario Besusso, Maria Teresa Zoia, Monica Rodolfo, Anna Maria Invernizzi, Masaru Taniguchi, Toshinori Nakayama, Mario Paolo Colombo, Sylvie Ménard, Andrea Balsari

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)151-158
Number of pages8
JournalJournal of Immunology
Volume169
Issue number1
Publication statusPublished - Jul 1 2002

ASJC Scopus subject areas

  • Immunology

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