title: Cognate memory CD4+ T cells generated with dendritic cell priming influence the expansion, trafficking, and differentiation of secondary CD8+ T cells and enhance tumor control.
abstract: CD4(+) T cells are known to provide support for the activation and expansion of primary CD8(+) T cells, their subsequent differentiation, and ultimately their survival as memory cells. However, the importance of cognate memory CD4(+) T cells in the expansion of memory CD8(+) T cells after re-exposure to Ag has been not been examined in detail. Using bone marrow-derived dendritic cells pulsed with cognate or noncognate MHC class I- and class II-restricted peptides, we examined whether the presence of memory CD4(+) T cells with the same Ag specificity as memory CD8(+) T cells influenced the quantity and quality of the secondary CD8(+) T cell response. After recombinant vaccinia virus-mediated challenge, we demonstrate that, although cognate memory CD4(+) T cells are not required for activation of secondary CD8(+) T cells, their presence enhances the expansion of cognate memory CD8(+) T cells. Cognate CD4(+) T cell help results in an approximate 2-fold increase in the frequency of secondary CD8(+) T cells in secondary lymphoid tissues, and can be accounted for by enhanced proliferation in the secondary CD8(+) T cell population. In addition, cognate memory CD4(+) T cells further selectively enhance secondary CD8(+) T cell infiltration of tumor-associated peripheral tissue, and this is accompanied by increased differentiation into effector phenotype within the secondary CD8(+) T cell population. The consequence of these improvements to the magnitude and phenotype of the secondary CD8(+) T cell response is substantial increase in control of tumor outgrowth.
authors.affiliation: Department of Pathology, Human Immune Therapy Center, University of Virginia Health System, Charlottesville, VA 22908, USA.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Hwang
authors.forename: John R
authors.initials: JR
authors.lastname: Lukens
authors.forename: Timothy N J
authors.initials: TN
authors.lastname: Bullock
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D002465:Cell Movement; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D018450:Disease Progression; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II