Retinal Antigen Specific Lymphocytes, Tcr-Gamma Delta T Cells and Cd5⁺B Cells Cultured from the Vitreous in Acute Sympathetic Ophthalmitis

Abstract

CD5+ B lymphocytes and TCR gamma-delta T lymphocytes, phenotypes implicated in the pathogenesis of autoimmune disease, were isolated from the vitreous in a case of acute sympathetic ophthalmitis. These cells were obtained using a method which allows the selective maintainance in vitro of in vivo activated T lymphocytes. Dual colour flow cytometry showed that after 3 days culture in IL-2 containing medium 61% of cells were CD5/CD19 + ve and 41% CD3/TCR gamma delta + ve. Of the total CD3 + ve population, 15% were gamma/delta negative. These cells formed a population which also responded in a proliferation assay to retinal antigens. Histologically the eye showed a marked mononuclear cell infiltration of the retina, ciliary body and choroid. Granulomatous lesions within the choroid contained lymphocytes, plasma cells and multinucleate giant cells. Immunocytochemistry showed lymphocyte populations to be predominantly CD2 + ve CD3 + ve T lymphocytes of the CD4 sub-set. Distribution of monocytes/macrophages throughout the lesions and restriction of B-lymphocytes to granulomata were all consistent with a DTH type reaction. Despite immunosuppressive therapy, the expression of activation antigens HLA-DR and ICAM-1 on infiltrating and resident ocular tissue cells was high, although IL-2 receptor (CD25) expression was virtually absent. Flow cytometric analysis of peripheral blood cells prior to treatment with Cyclosporin-A showed systemic activation of lymphocytes, with high levels of HLA-DR and CD25 expression and a raised CD4/CD8 ratio.

Dendritic cells: Vehicles for tolerance induction and prevention of autoimmune diseases

“…Although the mechanisms underlying this condition are not fully understood, it is thought that the release of intraocular protein-Ags in the traumatized eye evokes a T cellmediated (auto) immune reaction. These effector T cells will subsequently recognize similar Ags in the other eye leading to devastation of the non-traumatized eye (Liversidge et al, 1993). We consider it likely that trauma to the eye not only leads to the release of protein Ags, but also to the activation of DCs as we observed, in a mouse-system that disruption of anatomical barriers was strictly correlated with activation of CD11c + cells in draining lymph nodes.…”

“…Although, the mechanisms underlying these paraneoplastic events are not known, it is tempting to speculate that they would result from the generation of immunity following the release of danger or stress signals as a consequence of progressive tumor growth. Not only injury induced by tumors can trigger autoimmunity and destruction of otherwise healthy tissue, also other forms of trauma have been found in association with destruction of healthy tissues and induction of immunity as is exemplified by the clinical observation that trauma to one eye may cause destruction of the fellow eye, in a process called sympathetic ophthalmia (Liversidge et al, 1993). Although the mechanisms underlying this condition are not fully understood, it is thought that the release of intraocular protein-Ags in the traumatized eye evokes a T cellmediated (auto) immune reaction.…”

Maintenance of Immune Tolerance Depends on Normal Tissue Homeostasis

“…Although the mechanisms underlying this condition are not fully understood, it is thought that the release of intraocular protein-Ags in the traumatized eye evokes a T cell-mediated (auto) immune reaction. These effector T cells will subsequently recognize similar Ag in the other eye leading to devastation of the nontraumatized eye (31). We consider it likely that trauma to the eye not only leads to the release of protein Ag, but also to the activation of DC as we observed that phthisis was strictly correlated with activation of CD11c ϩ cells in DLN.…”

Antibody Production and In Vitro Behavior of CD27-Defined B-Cell Subsets: Persistent Hepatitis C Virus Infection Changes the Rules

“…Circulating HCV-specific plasma cells make a negligible contribution to the total serum antibodies because most HCVspecific ASC might be confined in a biological compartment that is not in equilibrium with the blood and therefore differs from that sustaining the nonspecific-antibody production. This is not surprising in view of the fact that under chronic inflammatory conditions, B cells bearing antigen-specific receptors can be stimulated to proliferate and differentiate into ASC within ectopic sites (34,38,72,74,75), including the germinal centers of intraportal lymphoid follicles (42,43,53,59).…”