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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Benghiat
Fleur Samantha
FS
Fonds National de la Recherche Scientifique, Belgium.
Craciun
Ligia
L
De Wilde
Virginie
V
Dernies
Tiffany
T
Kubjak
Carole
C
Lhomme
Frédéric
F
Goldman
Michel
M
Le Moine
Alain
A
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D016025:Bone Transplantation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D051858:Forkhead Transcription Factors / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D020381:Interleukin-17 / Q000096:biosynthesis*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous / Q000276:immunology; D014185:Transplantation, Isogeneic / Q000276:immunology
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D007519:Isoantigens