title: T and B cell recovery in arthritis adoptively transferred to SCID mice: antigen-specific activation is required for restoration of autopathogenic CD4+ Th1 cells in a syngeneic system.
abstract: T cell homeostasis is a physiological function of the immune system that maintains a balance in the numbers and ratios of T cells at the periphery. A self-MHC/self-peptide ligand can induce weak (covert) signals via the TCR, thus providing an extended lifespan for naive T cells. A similar mechanism is responsible for the restoration of immune homeostasis in severe lymphopenic conditions such as those following irradiation or chemotherapy, or upon transfer of lymphocytes to nu/nu or SCID mice. To date, the genetic backgrounds of donor and recipient SCID mice were unmatched in all autoimmune arthritis transfer experiments, and the recovery of lymphoid cells in the host has not been followed. In this study, we present the adoptive transfer of proteoglycan (PG)-induced arthritis using unseparated and T or B cell-depleted lymphocytes from arthritic BALB/c donors to genetically matched syngeneic SCID recipient mice. We demonstrate that selectively recovered lymphoid subsets determine the clinical and immunological status of the recipient. We found that when T cells were depleted (>98% depleted), B cells did not produce PG-specific anti-mouse (auto) Abs unless SCID mice received a second Ag (PG) injection, which promoted the recovery of Ag-specific CD4(+) Th1 cells. Reciprocally, as a result of B cell recovery, high levels of serum anti-PG Abs were found in SCID mice that received B cell-depleted (>99% depleted) T lymphocytes. Our results indicate a selective and highly effective cooperation between CD4(+) T cells and B lymphocytes that is required for the restoration of pathological homeostasis and development of autoimmune arthritis in SCID mice.
authors.affiliation: Section of Molecular Medicine, Departments of Orthopedic Surgery and Biochemistry, Section of Rheumatology, Department of Medicine, and Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Rush University, Chicago, IL 60612.
authors.forename: Tamás
authors.initials: T
authors.lastname: Bárdos
authors.forename: Katalin
authors.initials: K
authors.lastname: Mikecz
authors.forename: Alison
authors.initials: A
authors.lastname: Finnegan
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Tibor T
authors.initials: TT
authors.lastname: Glant
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D053674:Aggrecans; D000818:Animals; D000918:Antibody Specificity; D001169:Arthritis, Experimental / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D007519:Isoantigens / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011509:Proteoglycans / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology* / Q000637:transplantation
chemical_list: C508320:Acan protein, mouse; D053674:Aggrecans; D001323:Autoantibodies; D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D016326:Extracellular Matrix Proteins; D007519:Isoantigens; D037181:Lectins, C-Type; D011509:Proteoglycans