title: CD49b-dependent establishment of T helper cell memory.
abstract: CD4 T cells play a key role in immunological memory. We have demonstrated that professional memory CD4 T cells reside and rest in the bone marrow (BM). However, the molecular mechanisms of their establishment in the BM and their maintenance remain unclear. We here show that memory CD4 T cells express high levels of CD49b and that CD49b-deficient or -blocked memory CD4 T-cell precursors fail to migrate from blood into the marrow of the bone, and they especially fail to transmigrate through sinusoidal endothelial cells of the BM. In the marrow, memory CD4 T cells and the precursors contact stromal cells expressing collagen II that are specific ligands for CD49b. Interestingly, memory CD4 T cells on day 117 of an immune response also dock on IL-7(+)/collagen XI(+) stromal cells, whereas memory precursors on day 12 do not. These results indicate that the collagen receptor CD49b is required for the migration of memory CD4 T-cell precursors into their survival niches of the bone marrow.
authors.affiliation: 1] Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan [2] German Rheumatism Research Center Berlin, Berlin, Germany.
authors.forename: Asami
authors.initials: A
authors.lastname: Hanazawa
authors.forename: Koji
authors.initials: K
authors.lastname: Hayashizaki
authors.forename: Kenta
authors.initials: K
authors.lastname: Shinoda
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Max
authors.initials: M
authors.lastname: Löhning
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hara
authors.forename: Shizue
authors.initials: S
authors.lastname: Tani-ichi
authors.forename: Koichi
authors.initials: K
authors.lastname: Ikuta
authors.forename: Beate
authors.initials: B
authors.lastname: Eckes
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Koji
authors.initials: K
authors.lastname: Tokoyoda
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D015704:CD4 Antigens / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D024043:Collagen Type II / Q000378:metabolism; D024161:Collagen Type XI / Q000378:metabolism; D007156:Immunologic Memory / Q000235:genetics; D039421:Integrin alpha2 / Q000235:genetics / Q000378:metabolism*; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D057705:Transendothelial and Transepithelial Migration / Q000235:genetics
chemical_list: D015704:CD4 Antigens; D024043:Collagen Type II; D024161:Collagen Type XI; D039421:Integrin alpha2; D015851:Interleukin-7