|Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 1998 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1997 : ¥1,600,000 (Direct Cost : ¥1,600,000)
1 Our previous study demonstrated that both Thi and Th2 cytokines are involved in the development of lupus. In this study, to elucidate the complexity of cytokine regulation in the pathogenesis of autoimmunity in lupus, we first examined the role of IL-4 and IL-12. which play decisive roles In the development of Th2 and Thi, respectively, in NZB/W (B/W) Fl mice. Administration of mAb against either IL-4 or IL-12 before the onset of lupus could Inhibit the production of lgG anti-dsDNAAb. However, only anti-IL-4 mAb was effective In preventing the onset of lupus nephrltis. These results Indicate that both Th2 and Thi contribute to the lgG autoantibody production, and IL-4 is more critical. To further extend our understandings of Th2 development, we found that CDS6 costimulation plays a dominant role not only in the primary activation of Th2 cells but also in the secondary interaction between antigen primed Th2 cells and B cells. Next, we examined the contribution of B cell costimulatory
molecules such as CD19 and CD21 to the development of lupus, we found that blockade of both CD19 and CD21 exacerbated murine lupus. These results Indicated that CD19 and CD21 were negatively regulated the onset of lupus.
2 To clarify the contribution of other costimulatory pathway, we focused on TNF/TNFreceptor family. Initially, we found that Fas/FasL interaction is involved in the destruction of hair follicles which is a characteristic feature of cutaneous lupus. Next, we found that inappropriate expression of CD4OL elicited anti-self immune response.
OX4OL-0X40 Interaction and CD7O-CD27 interaction were involved in the development of cell-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. 3 Recent studies have indicated that some chemokine receptors are differentially expressed on T helper (Th) 1 and Th2 cells, our results indicated that differential expression of chemokine receptors plays a critical role for selective recruitment of pro-inflammatory T cells Into the joints of RA. Less