title: Cutting edge: CXCR4 is critical for CD8+ memory T cell homeostatic self-renewal but not rechallenge self-renewal.
abstract: Central memory (CM) CD8(+) T cells "remember" prior encounters because they maintain themselves through cell division in the absence of ongoing challenge (homeostatic self-renewal), as well as reproduce the CM fate while manufacturing effector cells during secondary Ag encounters (rechallenge self-renewal). We tested the consequence of conditional deletion of the bone marrow homing receptor CXCR4 on antiviral T cell responses. CXCR4-deficient CD8(+) T cells have impaired memory cell maintenance due to defective homeostatic proliferation. Upon rechallenge, however, CXCR4-deficient T cells can re-expand and renew the CM pool while producing secondary effector cells. The critical bone marrow-derived signals essential for CD8(+) T cell homeostatic self-renewal appear to be dispensable to yield self-renewing, functionally asymmetric cell fates during rechallenge.
authors: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors: Julie
authors: J
authors: Chaix
authors: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors: Simone A
authors: SA
authors: Nish
authors: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors: Wen-Hsuan W
authors: WH
authors: Lin
authors: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032;
authors: Nyanza J
authors: NJ
authors: Rothman
authors: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Rehabilitation and Regenerative Medicine, Columbia University, New York, NY 10032; and.
authors: Lei
authors: L
authors: Ding
authors: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors: E John
authors: EJ
authors: Wherry
authors: Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032; sreiner@columbia.edu.
authors: Steven L
authors: SL
authors: Reiner
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002999:Clone Cells; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019718:Receptors, CXCR4 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: C514936:CXCR4 protein, mouse; D019718:Receptors, CXCR4