| First Author | Balasa B | Year | 1997 |
| Journal | J Immunol | Volume | 159 |
| Issue | 9 | Pages | 4620-7 |
| PubMed ID | 9379064 | Mgi Jnum | J:43513 |
| Mgi Id | MGI:1097828 | Doi | 10.4049/jimmunol.159.9.4620 |
| Citation | Balasa B, et al. (1997) CD40 ligand-CD40 interactions are necessary for the initiation of insulitis and diabetes in nonobese diabetic mice. J Immunol 159(9):4620-7 |
| abstractText | The nonobese diabetic (NOD) mouse spontaneously develops T cell-dependent autoimmune diabetes. Here, we investigate the role of CD40 ligand (CD40L)-CD40 costimulation in the initiation and progression of this disease. Anti-CD40L mAb treatment of 3- to 4-wk-old NOD females (the age at which insulitis typically begins) completely prevented the insulitis and diabetes. In contrast, treatment of such mice with anti-CD40L at >9 wk of age did not inhibit the disease process. These results suggest that a costimulatory signal by CD40L is required early but not in the effector phase of disease development. Anti-CD40L treatment affected the priming of islet Ag-specific T cell responses in vivo. Cytokine analysis revealed a dramatic decrease in IFN-gamma and IL-2 release without a concomitant increase in IL-4 production by T cells from anti-CD40L-treated mice. Thus, anti-CD40L impaired the islet Ag-specific Th1 cell response in vivo, and the prevention of diabetes by anti-CD40L was not associated with switching of the response from a Th1 to a Th2 profile. Cotransfer of splenocytes from anti-CD40L-treated mice with splenocytes from diabetic NOD mice into NOD/scid mice did not inhibit the transfer of disease, indicating that anti-CD40L does not prevent the disease by inducing regulatory cells. Since anti-CD40L clearly prevented the insulitis by inhibiting the development and further accumulation of pathogenic Th1 cells to islets of Langerhans, we conclude that CD40L-CD40 costimulation is required for early events in the development of spontaneous autoimmune diabetes. |
