title: Dendritic cell-MHC class II and Itk regulate functional development of regulatory innate memory CD4+ T cells in bone marrow transplantation.
abstract: MHC class II (MHCII)-influenced CD4(+) T cell differentiation and function play critical roles in regulating the development of autoimmunity. The lack of hematopoietic MHCII causes autoimmune disease that leads to severe wasting in syngeneic recipients. Using murine models of bone marrow transplantation (BMT), we find that MHCII(-/-)→wild-type BMT developed disease, with defective development of innate memory phenotype (IMP, CD44(hi)/CD62L(lo)) CD4(+) T cells. Whereas conventional regulatory T cells are unable to suppress pathogenesis, IMP CD4(+) T cells, which include conventional regulatory T cells, can suppress pathogenesis in MHCII(-/-)→wild-type chimeras. The functional development of IMP CD4(+) T cells requires hematopoietic but not thymic MHCII. B cells and hematopoietic CD80/86 regulate the population size, whereas MHCII expression by dendritic cells is sufficient for IMP CD4(+) T cell functional development and prevention of pathogenesis. Furthermore, the absence of Tec kinase IL-2-inducible T cell kinase in MHCII(-/-) donors leads to preferential development of IMP CD4(+) T cells and partially prevents pathogenesis. We conclude that dendritic cells-MHCII and IL-2-inducible T cell kinase regulate the functional development of IMP CD4(+) T cells, which suppresses the development of autoimmune disorder in syngeneic BMTs.
authors.affiliation: Department of Microbiology & Immunology and Program in Infection & Pathobiology, Cornell University, Ithaca, NY, USA.
authors.forename: Weishan
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Microbiology & Immunology and Program in Infection & Pathobiology, Cornell University, Ithaca, NY, USA.|Huck Institutes of The Life Sciences and Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Huck Institutes of The Life Sciences and Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Microbiology & Immunology and Program in Infection & Pathobiology, Cornell University, Ithaca, NY, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Terri M
authors.initials: TM
authors.lastname: Laufer
authors.affiliation: Department of Microbiology & Immunology and Program in Infection & Pathobiology, Cornell University, Ithaca, NY, USA.
authors.forename: Avery
authors.initials: A
authors.lastname: August
mesh_terms: D000818:Animals; D001835:Body Weight; D016026:Bone Marrow Transplantation / Q000379:methods*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019041:L-Selectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D018960:Hyaluronan Receptors; D019041:L-Selectin; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase