Bum Seok Kim

CD4+CD25+ Regulatory T Cells Control the Severity of Viral Immunoinflammatory Lesions

CD4+CD25+ regulatory T cells (Treg) can inhibit a variety of autoimmune and inflammatory diseases, but their involvement in regulating virus-induced immunopathology is not known. We have evaluated the role of Treg in viral immunopathological lesion stromal keratitis. This frequent cause of human blindness results from a T cell-mediated immunoinflammatory response to HSV in the corneal stroma. The results show that lesions were significantly more severe if mice were depleted of Treg before infection. The Treg was also shown to modulate lesion expression induced by adoptive transfer of pathogenic CD4+ T cells in infected SCID recipients. The mechanism of Treg control of stromal keratitis involved suppressed antiviral immunity and impaired expression of the molecule required for T cell migration to lesion sites. Interestingly, Treg isolated from ocular lesions in nondepleted mice showed in vitro inhibitory effects involving IL-10, but were not very effective in established lesions. Our results decipher the in vivo role of Treg in a virus-induced immunopathology and imply that manipulation of regulatory cell function represents a useful approach to control viral-induced immunoinflammatory disease.

Gout Induced by Intoxication of Sodium Bicarbonate in Korean Native Broilers

Gout is a metabolic disorder that results in hyperuricemia and the deposition of positively birefringent monosodium urate crystals in various parts of the body. Intoxication of sodium bicarbonate (SBC) for 35 days in Korean native broilers was investigated. Sixty birds, aged 2 weeks, divided into 5 groups were exposed to excess SBC: 2 g/L (group A), 7.5 g/L (group B), 20 g/L (group C), 40 g/L (group D). Toxicopathological examination of all exposed birds revealed the manifestation of visceral and articular gout in group C, while birds of group D showed acute kidney damage with manifestation of excessive visceral gout. Interestingly, few birds in group D also showed signs of rare condition of acute articular gout. Dose-dependent increments in erythrocytic count, hematocrit values, and hemoglobin levels of the exposed birds were observed. Hypernatremia, hyperuricemia, hypokalemia, and hypochloremia were common findings among exposed birds. Microscopic examination of birds that manifested visceral gout revealed significant urate deposit, tubular necrosis, and tophi formation in renal interstitium. These findings provide a pathophysiological link that SBC intoxication may support hyperuricemia, which is an independent risk factor for gout and other renal dysfunctions. Further study is required to delineate the effect of lowering uric acid on progression of gout and other renal diseases.