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CD8⁺ Cytotoxic T-APC Stimulate Central Memory CD8⁺ T Cell Responses via Acquired Peptide-MHC Class I Complexes and CD80 Costimulation, and IL-2 Secretion¹

Research Unit, Saskatchewan Cancer Agency, Departments of Oncology, Microbiology, and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

We previously showed that naive CD4⁺ Th cells acquire peptide-MHC class I (pMHC I) and costimulatory molecules from OVA-pulsed dendritic cells (DC_OVA), and act as Th-APCs in stimulation of CD8⁺CTL responses. In this study, we further demonstrated that naive CD8⁺ cytotoxic T (Tc) cells also acquire pMHC I and costimulatory CD54 and CD80 molecules by DC_OVA stimulation, and act as Tc-APC. These Tc-APC can play both negative and positive modulations in antitumor immune responses by eliminating DC_OVA and neighboring Tc-APC, and stimulating OVA-specific CD8⁺ central memory T responses and antitumor immunity. Interestingly, the stimulatory effect of Tc-APC is mediated via its IL-2 secretion and acquired CD80 costimulation, and is specifically targeted to OVA-specific CD8⁺ T cells in vivo via its acquired pMHC I complexes. These principles could be applied to not only antitumor immunity, but also other immune disorders (e.g., autoimmunity).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Research Grants (MOP 79415 and 67230) from the Canadian Institute of Health Research (to J.X.).

² D.X. and S.H. made the same contribution in this study.

³ Address correspondence and reprint requests to Dr. Jim Xiang, Saskatoon Cancer Center, 20 Campus Drive, Saskatoon, Saskatchewan S7N 4H4, Canada. E-mail address: jxiang{at}scf.sk.ca

⁴ Abbreviations used in this paper: DC, dendritic cell; pMHC, peptide-MHC; pMHC II, pMHC class II; pMHC I, pMHC class I; DC_OVA, OVA-pulsed DC; KO, knockout; BM, bone marrow; Tc, cytotoxic T; Tc1, type 1 Tc; ECD, energy-coupled dye; Tm, memory T cell.

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