| First Author | Milich DR | Year | 1994 |
| Journal | J Immunol | Volume | 153 |
| Issue | 1 | Pages | 429-35 |
| PubMed ID | 7515930 | Mgi Jnum | J:18862 |
| Mgi Id | MGI:67084 | Doi | 10.4049/jimmunol.153.1.429 |
| Citation | Milich DR, et al. (1994) Soluble CTLA-4 can suppress autoantibody production and elicit long term unresponsiveness in a novel transgenic model. J Immunol 153(1):429-35 |
| abstractText | Activation of Ag-specific T cells often requires costimulatory signals in addition to the primary signal mediated through the TCR. The CD28-B7 interaction provides one important costimulatory signal. Previous studies have shown that a soluble CD28 homologue, CTLA4lg, binds B7 with high affinity and can inhibit CD28-B7-mediated costimulation in vitro and in vivo. In this study we examined the ability of soluble human CTLA4lg to inhibit autoantibody production in vivo. For this purpose we used a novel transgenic (Tg) model of autoantibody production. Hepatitis B eAg-expressing Tg mice can be induced to produce autoantibody to the circulating autoantigen (HBeAg) by the injection of a T cell recognition site that fails to elicit T cell tolerance in these mice. Autoimmunity in this model is quantitative because serum autoantibody and autoantigen concentration are inversely correlated and easily measurable by ELISA. In this system a single regimen of CTLA4lg treatment significantly suppressed primary autoantibody production and variably led to long term unresponsiveness. Furthermore, in vivo treatment with CTLA4lg inhibited both T cell activation and T cell-B cell interactions. |
