title: Function of CD4+CD3- cells in relation to B- and T-zone stroma in spleen.
abstract: Lymphocytes from lymphotoxin (LT) alpha-deficient mice, which lack segregation of their B- and T-cell areas, acquire normal organization following adoptive transfer into RAG-deficient recipients, identifying a non-B non-T cell in the segregation process. Here we show that a CD4+CD3- accessory cell is tightly associated with discrete VCAM-1-expressing stromal cells in B- and T-cell areas of the mouse spleen. CD4+CD3- cells express high levels of LTalpha, LTbeta, and tumor necrosis factor (TNF) alpha, which are the ligands for the LTbeta receptor and TNFR1 expressed by stromal cells. The expression of these ligands is functional, as transferring CD4+CD3- cells derived from either embryonic or adult tissues into LTalpha-deficient mice organizes B/T segregation and up-regulates CCL21 protein expression in areas where T cells are segregated from B cells. We propose that the function of CD4+CD3- cells is to form a link between primed CD4 T cells and the underlying stromal elements, creating distinct microenvironments in which they enable effector responses.
authors.affiliation: Medical Research Council, Centre for Immune Regulation, Institute for Biomedical Research, Birmingham Medical School, UK.
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.forename: Fiona M
authors.initials: FM
authors.lastname: McConnell
authors.forename: Fabrina M C
authors.initials: FM
authors.lastname: Gaspal
authors.forename: Andrea
authors.initials: A
authors.lastname: White
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Glanville
authors.forename: Vasilios
authors.initials: V
authors.lastname: Bekiaris
authors.forename: Lucy S K
authors.initials: LS
authors.lastname: Walker
authors.forename: Jorge
authors.initials: J
authors.lastname: Caamano
authors.forename: Eric
authors.initials: E
authors.lastname: Jenkinson
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
authors.forename: Peter J L
authors.initials: PJ
authors.lastname: Lane
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D017252:CD3 Complex; D015704:CD4 Antigens; D015496:CD4-Positive T-Lymphocytes; D002450:Cell Communication / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D017154:Stromal Cells / Q000166:cytology*; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D008233:Lymphotoxin-alpha