Migration of T cells from nearby inflammatory foci into antibody bound tissue: a relay of T cell and antibody actions in targeting native autoantigen.
We have reported that binding of antibody to native autoantigen is prerequisite for T cells to target the native antigen in murine autoimmune ovarian disease model (AOD). As a result, ovarian follicles, with target antigen ZP3 (Zona Pellucida 3), are destroyed. In this study, AOD was induced by co-transfer of ZP3-specific CD4(+)T cells and ZP3 antibody. ZP3 CD4(+)T cells, labeled with CFSE, were found to target macrophages in degenerated follicles to form inflammatory foci, which were composed of mainly endogenous CD4(+)T cells (85%). Only endogenous T cells in the foci, with increased CD69(+)expression, further migrated into antibody bound follicles. No F4/80 or MHC II(+)cells were found to co-migrate with the T cells or in follicles. Co-transfer of ZP3 T cell and antibody also induced (1) a transient PMN influx at early stage and (2) a dramatic increase in IL-1 beta expression coincident with the migration in the ovary. These results suggest that ZP3 antibody binding, only in the presence of ZP3 T cells, may cause an inflammatory change in follicles, which attract endogenous T cells from nearby inflammation. Thus, through a relay between T cell and antibody mediated mechanisms, native autoantigen is targeted and destroyed. This mechanism may explain the requirement of antibody in several T cell mediated autoimmune diseases.
Lou
Ya-Huan
YH
Department of Basic Science, Dental Branch, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. ylou@uth.tmc.edu
Borillo
Jason
J
D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology / Q000502:physiology; D004195:Disease Models, Animal; D004527:Egg Proteins / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D006080:Ovarian Follicle / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface; D000072216:Zona Pellucida Glycoproteins
D000906:Antibodies; D001324:Autoantigens; D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse