Adoptive transfer of nontransgenic mesenteric lymph node cells induces colitis in athymic HLA-B27 transgenic nude rats.
HLA-B27 transgenic (TG) rats develop spontaneous colitis when colonized with intestinal bacteria, whereas athymic nude (rnu/rnu) HLA-B27 TG rats remain disease free. The present study was designed to determine whether or not HLA-B27 expression on T cells is required for development of colitis after transfer of mesenteric lymph node (MLN) cells into rnu/rnu HLA-B27 recipients. Athymic nontransgenic (non-TG) and HLA-B27 TG recipients received MLN cells from either TG or non-TG rnu/+ heterozygous donor rats that contain T cells. HLA-B27 TG rnu/rnu recipients receiving either non-TG or TG MLN cells developed severe colitis and had higher caecal MPO and IL-1beta levels, and their MLN cells produced more IFN-gamma and less IL-10 after in vitro stimulation with caecal bacterial lysate compared to rnu/rnu non-TG recipients that remained disease free after receiving either TG or non-TG cells. Interestingly, proliferating donor TG T cells were detectable one week after adoptive transfer into rnu/rnu TG recipients but not after transfer into non-TG recipients. T cells from either non-TG or TG donors induce colitis in rnu/rnu TG but not in non-TG rats, suggesting that activation of effector T cells by other cell types that express HLA-B27 is pivotal for the pathogenesis of colitis in this model.
Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
F
F
Hoentjen
S L
SL
Tonkonogy
B
B
Liu
R B
RB
Sartor
J D
JD
Taurog
L A
LA
Dieleman
D019264:Adoptive Transfer; D000818:Animals; D030801:Animals, Genetically Modified; D001419:Bacteria / Q000276:immunology; D002432:Cecum / Q000276:immunology / Q000382:microbiology; D002457:Cell Extracts / Q000276:immunology; D049109:Cell Proliferation; D003092:Colitis / Q000209:etiology* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D015796:HLA-B27 Antigen / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000276:immunology; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D008643:Mesentery; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude
D002457:Cell Extracts; D016207:Cytokines; D015796:HLA-B27 Antigen; D007375:Interleukin-1; D009195:Peroxidase