Infectious Uveitis, Mechanisms, and Immunopathology

It is important to distinguish infectious uveitis from a noninfectious one for early treatment. Bacteria, viruses, fungi, parasites are the causes of infectious uveitis. Bacterial diseases causing uveitis are mainly syphilis, tuberculosis, Lyme disease, and brucellosis. HIV, HSV, VZV, CMV, EBV, measles, and rubella are frequent viral causes. The most common fungal uveitis causes are Candidiasis, Aspergillosis, Cryptococcosis, and Histoplasmosis. It is now widely accepted that uveitis is not caused by direct infectious agents and that microorganisms alter immüne response leading to autoimmune and inflammatory diseases. The mechanism observed in immunopathogenesis is the destruction of retinal visual cells due to an irreversible CD4 T cell response. The Th1 cells reach the target retinal tissue from the peripheral lymphoid system for specific retinal autoantigens and cause changes in photoreceptors, leading to an increase of Th1 cytokines by an inflammatory reaction in the uveitic eyes, whereas the cytokines of Th2 increase in the later stages. In addition to Th1 cells, Th17, regulator T cells, cytokines, autoantibodies, and neutrophils are also discussed in immunopathogenesis.

Bortezomib Inhibit Acute Graft-Versus-Host Disease Via Shifting the Combination of T Cells Subpopulations

Abstract 4709 Objective: Acute graft-versus-host disease (aGVHD) confines the wider application of allogeneic bone marrow transplantation (allo-BMT), but recently studies indicate that it is possible to reduce the incidence and severity of aGVHD while preserving the GVT by using bortezomib. In current study, we explored the changes of T cell subsets after allo-BMT administrated with bortezomib immediately, in order to establish the mechanism about bortezomib attenuation aGVHD. Materials and Methods: BALB/c mouse were injected of 0.5 mL PBS containing C57BL/6 2×107 nucleated BM cells plus 1×107 splenocytes followed a single dose of lethal total body irradiation (TBI, 0.7 Gy/min, 8.0 Gy) with or without bortezomib at 1.0 mg/kg. The level of CD4+ CD25+ Foxp3+ regulator T cells is quantified by flow cytometry, and the cytokine level of IL-2 and IL-4 is quantified by ELISA. Results: Bortezomib remarkably reduce aGVHD severity and prolonged the surviving time. Along with bortezomib injection, the level of CD4+ CD25+ Foxp3+ regulator T cell is significantly increased, the cytokine level of IL-2 is decreased but IL-4 is increased. Conclusion: Bortezomib inhibit aGVHD through shifting the combination of T cell subpopulations with up regulation CD4+CD25+ Foxp3+ regulator T cells lead to reset Th1/Th2 cytokine balance. Disclosures: No relevant conflicts of interest to declare.