Migration of T cells from nearby inflammatory foci into antibody bound tissue: a relay of T cell and antibody actions in targeting native autoantigen

• Published in: Journal of autoimmunity 2003-08, Vol.21 (1), p.27-35
• Main Authors: Lou, Ya-Huan, Borillo, Jason
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - immunology; Antibodies - metabolism; Autoantibody; Autoantigens - immunology; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; autoimmune ovarian disease; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD69 antigen; Cell Movement - immunology; Cell Movement - physiology; Disease Models, Animal; Egg Proteins - immunology; Experimental autoimmune ovarian disease; Female; General aspects; Immunopathology; Inflammation - immunology; Inflammation - metabolism; interleukin 1^b; Macrophages - metabolism; Medical sciences; Membrane Glycoproteins - immunology; Mice; Native autoantigen; Ovarian Follicle - immunology; Ovarian Follicle - metabolism; Receptors, Cell Surface; T cell; Zona Pellucida Glycoproteins
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/S0896-8411(03)00081-7

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-1β 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.