regulation of anthrax toxin-specific antibody titers by natural killer t cell-derived il-4 and ifnγ监管的炭疽toxin-specific抗体滴度自然杀伤t细胞衍生il - 4和ifnγ.pdfVIP

Regulation of Anthrax Toxin-Specific Antibody Titers by Natural Killer T Cell-Derived IL-4 and IFNc T. Scott Devera, Sunil K. Joshi, Lindsay M. Aye, Gillian A. Lang, Jimmy D. Ballard, Mark L. Lang* Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America Abstract Activation of Natural Killer-like T cells (NKT) with the CD1d ligand a-GC leads to enhanced production of anthrax toxin protective Ag (PA)-neutralizing Abs, yet the underlying mechanism for this adjuvant effect is not known. In the current study we examined the role of Th1 and Th2 type responses in NKT-mediated enhancement of antibody responses to PA. First, the contribution of IL-4 and IFNc to the production of PA-specific toxin-neutralizing Abs was examined. By immunizing C57Bl/6 controls IL-42/ 2 mice and IFNc2/ 2 mice and performing passive serum transfer experiments, it was observed that sera containing PA-specific IgG1, IgG2b and IgG2c neutralized toxin in vitro and conferred protection in vivo. Sera containing IgG2b and IgG2c neutralized toxin in vitro but were not sufficient for protection in vivo. Sera containing IgG1 and IgG2b neutralized toxin in vitro and conferred protection in vivo. IgG1 therefore emerged as a good correlate of protection. Next, C57Bl/6 mice were immunized with PA alone or PA plus a Th2-skewing a-GC derivative known as OCH. Neutralizing PA-specific IgG1 responses were modestly enhanced by OCH in C57Bl/6 mice. Conversely, IgG2b and IgG2c were considerably enhanced in PA/OCH-immunized IL-42/ 2 mice but did not confer protection. Finally, bone marrow chimeras were generated such that NKT cells were unable to express IL-4 or IFNc. NKT-derived IL-4 was required for OCH- enhanced primary IgG1 re