T cells, but not thymic exposure to HLA-B27, are required for the inflammatory disease of HLA-B27 transgenic rats.
Rats transgenic for the human MHC class I gene HLA-B27 are susceptible to a spontaneous multisystem inflammatory disease that resembles human B27-associated disease. This disease requires a high level of expression of the B27 transgene product in cells of hemopoietic origin and can be adoptively transferred to B27 transgenic or nontransgenic rats by transplantation of bone marrow (BM) or fetal liver (FL) cells. To investigate the role played by T cells and the thymus in the disease process, we produced congenitally athymic rnu/rnu F344 rats carrying the disease-prone B27 transgenic locus of the 33-3 line. Transgenic nude rats were protected from disease manifestations. This protection was abated by reconstitution with T cells from euthymic donors of the 33-3 line, with CD4 T cells being more efficient than CD8 T cells in transferring disease. Lethally irradiated, adult-thymectomized (ATX), nontransgenic recipients reconstituted with intact BM, T cell-depleted BM, FL, or nude BM from syngeneic disease-prone lines all developed disease. Pretreatment of the ATX nontransgenic recipients to deplete T cells enhanced the subsequent transferred disease. The inflammatory disease of B27 transgenic rats is thus T cell-dependent. The relevant T cells do not need to encounter B27 in the thymus, and residual radioresistant and/or extrathymically derived host T cells are sufficient to mediate the adoptively transferred disease. The data are most consistent with a model of B27-mediated disease arising from a failure of tolerance and requiring a population of CD4 T cells.
Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235, USA.
M
M
Breban
J L
JL
Fernández-Sueiro
J A
JA
Richardson
R R
RR
Hadavand
S D
SD
Maika
R E
RE
Hammer
J D
JD
Taurog
D000818:Animals; D030801:Animals, Genetically Modified; D001168:Arthritis / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018956:CD5 Antigens / Q000276:immunology; D003106:Colon / Q000473:pathology; D003872:Dermatitis / Q000276:immunology; D003967:Diarrhea / Q000276:immunology; D004195:Disease Models, Animal; D015796:HLA-B27 Antigen / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive; D007249:Inflammation / Q000276:immunology*; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D009920:Orchitis / Q000276:immunology; D011828:Radiation Chimera; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011923:Rats, Nude; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D018956:CD5 Antigens; D015796:HLA-B27 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta