TY - JOUR
T1 - Absence of the CD1 molecule up-regulates antitumor activity induced by CpG oligodeoxynucleotides in mice
AU - Sfondrini, Lucia
AU - Besusso, Dario
AU - Zoia, Maria Teresa
AU - Rodolfo, Monica
AU - Invernizzi, Anna Maria
AU - Taniguchi, Masaru
AU - Nakayama, Toshinori
AU - Colombo, Mario Paolo
AU - Ménard, Sylvie
AU - Balsari, Andrea
PY - 2002/7/1
Y1 - 2002/7/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 12077240
AN - SCOPUS:0036644072
VL - 169
SP - 151
EP - 158
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -