Inhibition of CD8+ T cell-derived CD40 signals is necessary but not sufficient for Foxp3+ induced regulatory T cell generation in vivo.

Journal article

Current models of CD4(+) T cell help suggest a major role for CD154 binding to CD40 expressed on dendritic cells, with a lesser role for direct T:T interactions via CD40 expressed on CD8(+) T cells. However, the contribution of CD8(+) T cell-derived CD40 signals during the donor-reactive T cell response to a transplant has never been studied. In this study, we examined the graft-rejection kinetics and CD4(+) and CD8(+) donor-reactive T cell responses under conditions in which CD40 was genetically ablated only on APC, as well as under conditions in which CD40 was genetically ablated only on donor-reactive CD8(+) T cells. Our results revealed a significant role for CD8(+) T cell-expressed CD40 in the augmentation of donor-reactive CD8(+) T cell responses following transplantation and showed that CD40 expressed on CD8(+) T cells must be inhibited to allow conversion of CD4(+) T cells into induced regulatory T cells. Thus, this study identifies a major role for CD8(+) T cell-derived CD40 signals as a critical switch factor that both promotes optimal differentiation of cytokine-producing CD8(+) effector T cell responses and inhibits the differentiation of Ag-specific Foxp3(+) induced regulatory T cells in vivo.

Authors: Liu, D; Ferrer, I; Konomos, M; Ford, M

• Journal: Journal of Immunology
• Volume: 191
• Issue: 4
• Pages: 1957-1964
• Publication date: 2013-08-01
• DOI: 10.4049/jimmunol.1300267
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Antigens, CD40; Adoptive Transfer; CD40 Ligand; Transplantation Tolerance; Forkhead Transcription Factors; Mice; Lymphocyte Activation; T-Lymphocytes, Regulatory; Listeria monocytogenes; Animals; Epitopes, T-Lymphocyte; Dendritic Cells; Allografts; Mice, Inbred C57BL; T-Lymphocyte Subsets; Ovalbumin; Antigen Presentation; CD4-Positive T-Lymphocytes; Recombinant Proteins; Listeriosis; Skin Transplantation; CD8-Positive T-Lymphocytes