CD8+ cytotoxic T-APC stimulate central memory CD8+ T cell responses via acquired peptide-MHC class I complexes and CD80 costimulation, and IL-2 secretion.
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).
Xia
Dajing
D
Research Unit, Saskatchewan Cancer Agency, Saskatoon, Saskatchewan, Canada.
Hao
Siguo
S
Xiang
Jim
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D011485:Protein Binding
D018122:B7-1 Antigen; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D010455:Peptides; D018799:Intercellular Adhesion Molecule-1; D010047:Ovalbumin