title: Type II membrane protein CD69 regulates the formation of resting T-helper memory.
abstract: Memory T-helper (Th) lymphocytes are crucial for the maintenance of acquired immunity to eliminate infectious pathogens. We have previously demonstrated that most memory Th lymphocytes reside and rest on stromal niches of the bone marrow (BM). Little is known, however, regarding the molecular basis for the generation and maintenance of BM memory Th lymphocytes. Here we show that CD69-deficient effector CD4 T lymphocytes fail to relocate into and persist in the BM and therefore to differentiate into memory cells. Consequently, CD69-deficient CD4 T cells fail to facilitate the production of high-affinity antibodies and the generation of BM long-lived plasma cells in the late phase of immune responses. Thus, CD69 is critical for the generation and maintenance of professional memory Th lymphocytes, which can efficiently help humoral immunity in the late phase. The deficit of immunological memory in CD69-deficient mice also highlights the essential role of BM for the establishment of Th memory.
authors.affiliation: Department of Immunology, Graduate School of Medicine,  Chiba University, Chiba 260-8670,  Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Shinoda
authors.forename: Koji
authors.initials: K
authors.lastname: Tokoyoda
authors.forename: Asami
authors.initials: A
authors.lastname: Hanazawa
authors.forename: Koji
authors.initials: K
authors.lastname: Hayashizaki
authors.forename: Sandra
authors.initials: S
authors.lastname: Zehentmeier
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hosokawa
authors.forename: Chiaki
authors.initials: C
authors.lastname: Iwamura
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Damon J
authors.initials: DJ
authors.lastname: Tumes
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D049452:Green Fluorescent Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D000099192:CD69 Antigens