CD4+ T cells sensitized by vascular smooth muscle induce vasculitis, and interferon gamma is critical for the initiation of vascular pathology.
Primary vasculitis is the result of idiopathic inflammation in blood vessel walls. T cells are believed to play a critical role, but the nature of the pathological T-cell response remains obscure. In this study, we provide evidence that CD4(+) T lymphocytes, activated in the presence of syngeneic vascular smooth muscle cells, were sufficient to induce vasculitic lesions after adoptive transfer to recipient mice. Additionally, the disease is triggered in the absence of antibodies in experiments in which both the donors of stimulated lymphocytes and the transfer recipients were mice that were deficient in B cells. Tracking and proliferation of the transferred cells and their cytokine profiles were assessed by fluorescence tagging and flow cytometry. Proliferating CD4(+) T cells were evident 3 days after transfer, corresponding to the occurrence of vasculitic lesions in mouse lungs. The transferred T lymphocytes exhibited Th1 and Th17 cytokine profiles and minimal Th2. However, 1 week after vasculitis induction, effector functions could be successfully recalled in Th1 cells, but not in Th17 cells. Additionally, in the absence of constitutive interferon-γ expression, T cells sensitized by vascular smooth muscle cells failed to induce vasculitis. In conclusion, our results show that Th1 cells play a key role in eliciting vasculitis in this murine model and that induction of the disease is possible in the absence of pathogenic antibodies.
School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53705, USA.
Dana Carina
DC
Baiu
Matyas
M
Sandor
Michael
M
Hart
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014185:Transplantation, Isogeneic; D014657:Vasculitis / Q000276:immunology / Q000473:pathology*
D007371:Interferon-gamma