title: Expansion of regulatory CD8+ CD25+ T cells after neonatal alloimmunization.
abstract: Transplantation tolerance induced by neonatal injection of semi-allogeneic spleen cells is associated with a pathological syndrome caused by T helper type 2 (Th2) differentiation of donor-specific CD4(+) T lymphocytes. We have shown previously that this Th2-biased response is inhibited by host CD8(+) T cells. Herein, we demonstrate that upon neonatal immunization with (A/J × BALB/c)F(1) spleen cells, BALB/c mice expand a population of CD8(+) T cells expressing both CD25 and forkhead box P3 (FoxP3) markers. In this setting, CD8(+) CD25(+) T cells predominantly produce interferon (IFN)-γ and interleukin (IL)-10 and are efficient in controlling IL-4, IL-5 and IL-13 production by donor-specific CD4(+) T cells in vitro. CD8(+) FoxP3(-) T cells are single producers of IFN-γ or IL-10, whereas CD8(+) FoxP3(+) T cells are double producers of IFN-γ and IL-10. We further demonstrate that IFN-γ and IL-10 are two major cytokines produced by CD8(+) T cells involved in the in vivo regulation of Th2-type pathology. In this setting, we conclude that neonatal alloimmunization induces the expansion of several regulatory CD8(+) T cells which may control Th2 activities via IFN-γ and IL-10.
authors.affiliation: Institut d'Immunologie Médicale, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Adams
authors.forename: A
authors.initials: A
authors.lastname: Dubois
authors.forename: S
authors.initials: S
authors.lastname: Delbauve
authors.forename: I
authors.initials: I
authors.lastname: Debock
authors.forename: F
authors.initials: F
authors.lastname: Lhommé
authors.forename: M
authors.initials: M
authors.lastname: Goldman
authors.forename: V
authors.initials: V
authors.lastname: Flamand
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000473:pathology; D013163:Splenomegaly / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous; D001613:beta 2-Microglobulin / Q000235:genetics
chemical_list: D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D001613:beta 2-Microglobulin; D016753:Interleukin-10; D007073:Immunoglobulin E; D007371:Interferon-gamma