title: Contribution of 4-1BBL on radioresistant cells in providing survival signals through 4-1BB expressed on CD8⁺ memory T cells in the bone marrow.
abstract: The persistence of memory lymphocytes is a critical feature of adaptive immunity. The TNF family ligand 4-1BBL supports the antigen-independent survival of CD8⁺ memory T cells. Here, we show that mice lacking 4-1BB only on αβ T cells show a similar defect in CD8⁺ T-cell recall responses, as previously shown in 4-1BBL-deficient mice. We show that 4-1BB is selectively expressed on BM CD8⁺ but not CD4⁺ memory T cells of unimmunized mice. Its ligand, 4-1BBL, is found on VCAM-1⁺ stromal cells, CD11c⁺ cells, and a Gr1(lo) myeloid population in unimmunized mice. Adoptive transfer of in vitro generated memory T cells into mice lacking 4-1BBL only on radioresistant cells recapitulates the defect in CD8⁺ T-cell survival seen in the complete knockout mice, with smaller effects of 4-1BBL on hematopoietic cells. In BM, adoptively transferred DsRed CD8⁺ memory T cells are most often found in proximity to VCAM-1⁺ cells or Gr1⁺ cells, followed by B220⁺ cells and to a much lesser extent near CD11c⁺ cells. Thus, a VCAM-1⁺CD45(-) stromal cell is a plausible candidate for the radioresistant cell that provides 4-1BBL to CD8⁺ memory T cells in the BM.
authors.affiliation: Department of Immunology, University of Toronto, Toronto, ON, Canada.
authors.forename: Gloria H Y
authors.initials: GH
authors.lastname: Lin
authors.forename: Fanny
authors.initials: F
authors.lastname: Edele
authors.forename: Achire N
authors.initials: AN
authors.lastname: Mbanwi
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wortzman
authors.forename: Laura M
authors.initials: LM
authors.lastname: Snell
authors.forename: Mariana
authors.initials: M
authors.lastname: Vidric
authors.forename: Katrin
authors.initials: K
authors.lastname: Roth
authors.forename: Anja E
authors.initials: AE
authors.lastname: Hauser
authors.forename: Tania H
authors.initials: TH
authors.lastname: Watts
mesh_terms: D053330:4-1BB Ligand / Q000235:genetics / Q000276:immunology*; D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D011836:Radiation Tolerance / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D018183:Transplantation Chimera; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology*
chemical_list: D053330:4-1BB Ligand; D012367:RNA, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019010:Vascular Cell Adhesion Molecule-1