title: Control of the development of CD8αα+ intestinal intraepithelial lymphocytes by TGF-β.
abstract: The molecular mechanisms that direct the development of TCRαβ+CD8αα+ intestinal intraepithelial lymphocytes (IELs) are not thoroughly understood. Here we show that transforming growth factor-β (TGF-β) controls the development of TCRαβ+CD8αα+ IELs. Mice with either a null mutation in the gene encoding TGF-β1 or T cell-specific deletion of TGF-β receptor I lacked TCRαβ+CD8αα+ IELs, whereas mice with transgenic overexpression of TGF-β1 had a larger population of TCRαβ+CD8αα+ IELs. We observed defective development of the TCRαβ+CD8αα+ IEL thymic precursors (CD4⁻CD8⁻TCRαβ+CD5+) in the absence of TGF-β. In addition, we found that TGF-β signaling induced CD8α expression in TCRαβ+CD8αα+ IEL thymic precursors and induced and maintained CD8α expression in peripheral populations of T cells. Our data demonstrate a previously unrecognized role for TGF-β in the development of TCRαβ+CD8αα+ IELs and the expression of CD8α in T cells.
authors.affiliation: Mucosal Immunology Unit, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Konkel
authors.forename: Takashi
authors.initials: T
authors.lastname: Maruyama
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Carpenter
authors.forename: Yumei
authors.initials: Y
authors.lastname: Xiong
authors.forename: Brian F
authors.initials: BF
authors.lastname: Zamarron
authors.forename: Bradford E
authors.initials: BE
authors.lastname: Hall
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
authors.forename: Pin
authors.initials: P
authors.lastname: Zhang
authors.forename: Remy
authors.initials: R
authors.lastname: Bosselut
authors.forename: WanJun
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1