title: Adaptive Immune-like γ/δ T Lymphocytes Share Many Common Features with Their α/β T Cell Counterparts.
abstract: To better apprehend γ/δ T cell biological functions in the periphery, it appears crucial to identify markers highlighting the existence of distinct phenotypic and functional γ/δ T cell subsets. Interestingly, the expression of CD44 and Ly-6C subdivides murine peripheral γ/δ T cells into several subsets, with Ly-6C(-) CD44(hi) γ/δ T cells corresponding to the IL-17-producing CD27(-) γ/δ T cell subset exhibiting innate-like features. By comparing the other subsets to naive and memory CD8(+) α/β T cells, in this study, we show that Ly-6C(- or +) CD44(lo) and Ly-6C(+)CD44(hi) γ/δ T cells greatly resemble, and behave like, their CD8(+) α/β T cell counterparts. First, like memory CD8(+) α/β T cells, Ly-6C(+)CD44(hi) γ/δ T cells are sparse in the thymus but largely increased in proportion in tissues. Second, similarly to naive CD8 α/β T cells, CD44(lo) γ/δ T cells are poorly cycling in vivo in the steady state, and their proportion declines with age in secondary lymphoid organs. Third, CD44(lo) γ/δ T cells undergo spontaneous proliferation and convert to a memory-like Ly-6C(+)CD44(hi) phenotype in response to lymphopenia. Finally, CD44(lo) γ/δ T cells have an intrinsic high plasticity as, upon appropriate stimulation, they are capable of differentiating nonetheless into Th17-like and Th1-like cells but also into fully functional Foxp3(+) induced regulatory T cell-like γ/δ T cells. Thus, peripheral CD27(+) γ/δ T cells, commonly considered as a functionally related T cell compartment, actually share many common features with adaptive α/β T cells, as both lineages include naive-like and memory-like lymphocytes with distinct phenotypic, functional, and homeostatic characteristics.
authors.affiliation: Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris 75014, France; INSERM, U1016, Cochin Institute, Paris 75014, France; and Cochin Institute, Paris Descartes University, Paris 75014, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Lombes
authors.affiliation: Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris 75014, France; INSERM, U1016, Cochin Institute, Paris 75014, France; and Cochin Institute, Paris Descartes University, Paris 75014, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Durand
authors.affiliation: Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris 75014, France; INSERM, U1016, Cochin Institute, Paris 75014, France; and Cochin Institute, Paris Descartes University, Paris 75014, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Charvet
authors.affiliation: Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris 75014, France; INSERM, U1016, Cochin Institute, Paris 75014, France; and Cochin Institute, Paris Descartes University, Paris 75014, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Rivière
authors.affiliation: Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris 75014, France; INSERM, U1016, Cochin Institute, Paris 75014, France; and Cochin Institute, Paris Descartes University, Paris 75014, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Bonilla
authors.affiliation: Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris 75014, France; INSERM, U1016, Cochin Institute, Paris 75014, France; and Cochin Institute, Paris Descartes University, Paris 75014, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Auffray
authors.affiliation: Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris 75014, France; INSERM, U1016, Cochin Institute, Paris 75014, France; and Cochin Institute, Paris Descartes University, Paris 75014, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lucas
authors.affiliation: Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Paris 75014, France; INSERM, U1016, Cochin Institute, Paris 75014, France; and Cochin Institute, Paris Descartes University, Paris 75014, France bruno.martin@inserm.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Martin
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006706:Homeostasis; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000096:biosynthesis; D008231:Lymphopenia / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
chemical_list: D000950:Antigens, Ly; D018960:Hyaluronan Receptors; D020381:Interleukin-17; C494192:Ly-6C antigen, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7