title: Characterization of mouse CD4 T cell subsets defined by expression of KLRG1.
abstract: The mouse killer cell lectin-like receptor G1 (KLRG1) is an inhibitory receptor known to be expressed on a subset of NK cells and antigen-experienced CD8 T cells. Here, we have characterized expression of KLRG1 on CD4+ T cells from normal mice. While a polyclonal TCR repertoire suggests thymic origin of KLRG1+ CD4+ cells, KLRG1 expression was found to be restricted to peripheral CD4+ T cells. Based on phenotypic analyses, a minority of KLRG1+ CD4+ cells are effector/memory cells with a proliferative history. The majority of KLRG1+ CD4+ cells are, however, bona fide Treg cells that depend on IL-2 and/or CD28 and express both FoxP3 and high levels of intracellular CD152. KLRG1-expressing Treg are contained within the CD38+ subset but are only partially overlapping with the CD25+ CD4+ Treg subset. In functional assays, KLRG1+ CD4+ cells were anergic to TCR stimulation with respect to proliferation, and sorted KLRG1+ CD25+ CD4+ cells were equal or superior to KLRG1+ CD25- CD4+ cells, which were more potent than KLRG1- CD25+ CD4+ cells in suppressing responder cell proliferation. Together, our results demonstrate that KLRG1 expression defines novel and distinctive subsets of senescent effector/memory and potent regulatory CD4+ T cells.
authors.affiliation: University of Würzburg, Institute for Virology and Immunobiology, Würzburg, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Beyersdorf
authors.forename: Xin
authors.initials: X
authors.lastname: Ding
authors.forename: Julia K
authors.initials: JK
authors.lastname: Tietze
authors.forename: Thomas
authors.initials: T
authors.lastname: Hanke
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D018106:CD28 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000145:classification* / Q000276:immunology; D060908:CTLA-4 Antigen; D019070:Cell Lineage; D016922:Cellular Senescence; D051858:Forkhead Transcription Factors / Q000032:analysis; D007156:Immunologic Memory; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000172:deficiency / Q000502:physiology; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000032:analysis*; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000145:classification* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000145:classification* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic