A small population of vasculitogenic T cells expands and has skewed T cell receptor usage after culture with syngeneic smooth muscle cells.
Adoptive transfer of lymphocytes co-cultured with syngeneic smooth muscle (SM) cells to healthy recipient mice results in vasculitic lesions predominantly in post-capillary venules. The present study focuses on the mechanisms by which the disease-inducing CD4(+) T cells are generated in co-culture of lymphocytes with SM cells. Microvascular SM cells provide survival signals to both CD4(+) and CD8(+) naïve syngeneic T cells and can activate only a limited range of CD4(+) T lymphocytes in culture. Additionally, approximately 0.4% of the original CD4(+) T cells divide at least twice in co-culture with SM cells. Survival of CD4(+) T cells in co-culture is dependent on a TCR mediated process, since transgenic CD4 (+)cells with a unique specificity for a non-murine peptide do not survive in culture with SM. Analysis of TCR Vbeta shows no superantigen activation of T cells following co-culture with SM cells. Spectratype analysis of TCR Vbeta Jbeta segment usage reveals a skewage in the TCR repertoire of T cells co-cultured with SM, and also of T cells from vasculitic lung. These results are consistent with a specific immune response of pathogenic T cells against one or more activating antigenic determinants of the microvascular SM cells, in contrast to non-specific cytokine activation.
Swanson
Brad J
BJ
Department of Pathology and Laboratory Medicine, 6152 MSC University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.
Baiu
Dana C
DC
Sandor
Matyas
M
Fabry
Zsuzsa
Z
Hart
Michael N
MN
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D018920:Coculture Techniques; D022801:Complementarity Determining Regions / Q000276:immunology; D004195:Disease Models, Animal; D051379:Mice; D008807:Mice, Inbred BALB C; D009131:Muscle, Smooth, Vascular / Q000276:immunology* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D014657:Vasculitis / Q000209:etiology / Q000276:immunology*
D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta