Role of HTLV-I on pathegenesis of Sjogren's syndrome

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Previously we have reported a high prevalence of HTLV-1 iiifcction in Sjogren's syndrome (SS). At first in the present study, we investigated whether SS was complicated with HTLV-l associated myclopathy (HAM). According to thc preliminary criteria for SS proposed by the European Community, definitive SS WaS (liagnosed in 6 of 10 patients. There was no significant difference in the prevalence of autoantibodies including rheumatoid factor, anti-nuclear antibody and anti-SS-A (Ro) antibody among HAM patients with definitive SS, HTLV-1 Seropositive and HTLV-I seronegative SS patients.Next, we ditermine the possible involvement of Fas and its ligand in salivary gland destruction. Several duetal epithelial cells. Acinal epithelial cells were also double-positive with Fas and FasL, aothough expression of FasL was localized at their apical border, suggest that apoptosis of acinal epithelial cells was mediated by FasL derived from either acinal epithelial cells or infiltrating mononuclear cells … More . Interestingly, Fas expression in ductal epithelial cells was licalized around the luman side of the ducts, indicating that FasL secreted from acinal epithelial cells may induce Fas-mediated apoptosis of ductal epithelial cells.We determined the role of interactions between CD4O and CD4O ligand (CD4OL) in these infiltrating lymphocytes on B cell differentiation. A clear expression of CD4OL and CD4O in infiltrating lymphocytes was demonstrated. The expression of Bcl-2 andBcl-X was colocalized with that of CD4O determined by mirror section technique. BcI-X was abduntly expressed on infiltrating mononuclear cells, but Bax expression was relatively less than that of Bc1-2 or Bc1-X.These findings suggest that signaling through CD4 O by means CD4OL increases the expression of Bcl-2 and Bcl-X in infiltrating lymphocytes, providing the resistance against apoptosis. Present results were commonly observed in SS patients irrespective of HTLV-I seropositivety.We examined the importance of in inhibiting activation of the caspase cascade, which operates a regulatory loop that prevent apoptosis. Apoptosis was induced in Jurkat cells and JPX-9 cells which Tax-expression plasmid pMAX-Neo is stably transfected in Jurkat by NF-_KB inhibitor. Preincubation of JPX-9 cells with CdCI_2, which induced Tax expression, significantly inhibited both the activation of caspases and apoptosis. The results suggest that apoptosis is initiated via activation of caspase cascade by inhibiting the activation. Furthermore, activation of NF-_KB via Tax protein in HTLV-I infected cells renders the cells resistant against apoptosis, resulting in an increase of cytokine production and cell proliferation, one of the proposed mechanisms that promotes autoimmune disorders such as Sjogren's syndrome (SS) found in HTLV-I seropositive subjects.Finally, we examined the mechanisms by which high-dose steroid and FK506 exerts the immunosuppressive actions. Peripheral blood T cells from normal subjects underwent DNA fragmentation following the in vitro exposure to 10^-^7M of dexametllasone for 30 min. FK506 synergistically enhanced this dexaniethazone-mediated apoptosis of human peripheral blood T cells. These results indicate that the induction of peripheral blood T cell apoptosis is an important mechanism contributing to the immunosuppression achieved by steroid and FK5O6. Less