title: Regulation of secondary antigen-specific CD8(+) T-cell responses by natural killer T cells.
abstract: The physiologic function of natural killer T (NKT) cells in adaptive immunity remains largely unknown because most studies have used NKT cell agonists. In the present study, the role of NKT cells during the secondary effector phase was investigated separately from the primary immunization phase via adoptive transfer of differentiated effector T cells into naive recipients. We found that secondary antitumor CD8(+) T-cell responses were optimal when NKT cells were present. Tumor-specific CD8(+) effector T cells responded less strongly to tumor cell challenge in NKT cell-deficient recipients than in recipients with intact NKT cells. NKT cell-mediated enhancement of the secondary antitumor CD8(+) T-cell response was concurrent with increased number and activity of tumor-specific CD8(+) T cells. These findings provide the first demonstration of a direct role for NKT cells in the regulation of antigen-specific secondary T-cell responses without the use of exogenous NKT cell agonists such as alpha-galactosylceramide (alpha-GalCer). Furthermore, forced activation of NKT cells with alpha-GalCer during the secondary immune response in suboptimally immunized animals enhanced otherwise poor tumor rejection responses. Taken together, our findings strongly emphasize the importance of NKT cells in secondary CD8(+) T-cell immune responses.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Sungbukku Anamdong, Seoul, Korea.
authors.forename: Changwan
authors.initials: C
authors.lastname: Hong
authors.forename: Hyunji
authors.initials: H
authors.lastname: Lee
authors.forename: Yoon-Kyung
authors.initials: YK
authors.lastname: Park
authors.forename: Junghoon
authors.initials: J
authors.lastname: Shin
authors.forename: Sundo
authors.initials: S
authors.lastname: Jung
authors.forename: Hoyeon
authors.initials: H
authors.lastname: Kim
authors.forename: Seokmann
authors.initials: S
authors.lastname: Hong
authors.forename: Se-Ho
authors.initials: SH
authors.lastname: Park
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005434:Flow Cytometry; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics
chemical_list: D055610:Antigens, CD1d; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin