IL-17 production elicited by allo-major histocompatibility complex class II recognition depends on CD25posCD4pos T cells

• Published in: Transplantation Vol. 85; no. 7; p. 943
• Main Authors: Benghiat, Fleur Samantha, Craciun, Ligia, De Wilde, Virginie, Dernies, Tiffany, Kubjak, Carole, Lhomme, Frédéric, Goldman, Michel, Le Moine, Alain
• Format: Journal Article
• Language: English
• Published: United States 15.04.2008
• Subjects: Animals; Bone Marrow Cells - immunology; Bone Transplantation - immunology; CD4-Positive T-Lymphocytes - immunology; Cell Division - immunology; Dendritic Cells - immunology; Dendritic Cells - transplantation; Forkhead Transcription Factors - immunology; Histocompatibility Antigens Class II - immunology; Interleukin-17 - biosynthesis; Interleukin-2 Receptor alpha Subunit - immunology; Isoantigens - immunology; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred C57BL; Transplantation, Homologous - immunology; Transplantation, Isogeneic - immunology
• ISSN: 0041-1337
• DOI: 10.1097/TP.0b013e31816a5ae7

Interleukin (IL)-17 is involved in autoimmune inflammatory disorders and naturally occurring CD25pos regulatory T cells were shown to promote IL-17 synthesis. Because IL-17 is overproduced in certain types of allograft rejection, it is important to characterize the cells responsible for IL-17 synthesis and to define how IL-17 is regulated during alloimmune responses. Splenic CD4pos T cells were isolated from C57BL/6 mice and fractionated according to CD25 expression. T cells were stimulated by major histocompatibility complex class II-mismatched bone marrow-derived dendritic cells from bm12 mice, either immature or made mature by exposure to lipopolysaccharide. To track T cell populations, CD25negCD4pos and CD25posCD4pos were isolated from Thy1.1 and congenic Thy1.2 mice, respectively. Cell proliferation was quantified by CFSE dilution. IL-17-producing cells and FOXP3pos cells were enumerated by intracytoplasmic staining and cytokine levels in culture supernatants were measured by ELISA. Addition of CD25posCD4pos T cells to CD25negCD4pos T cells inhibited IL-2, interferon-[gamma], and IL-13 production but promoted IL-17 synthesis on stimulation by allogenic immature DC. In this setting, IL-17 originated from CD25intCD4posFOXP3neg memory T cells, which depend on IL-2 to produce IL-17. Alloreactive CD25negCD4pos T cells were also induced to produce IL-17 when stimulated by mature DC in the presence of CD25highCD4posFOXP3pos T cells. We conclude that (1) the cellular source of IL-17 during an antiallo major histocompatibility complex class II response depends on the maturation status of allogenic DC, (2) whereas suppressing Th1 and Th2 cytokine synthesis, naturally occurring regulatory T cells, allow IL-17 production by alloreactive CD4pos T cells.