| First Author | Yu XZ | Year | 2000 |
| Journal | J Immunol | Volume | 164 |
| Issue | 9 | Pages | 4564-8 |
| PubMed ID | 10779758 | Mgi Jnum | J:61707 |
| Mgi Id | MGI:1355446 | Doi | 10.4049/jimmunol.164.9.4564 |
| Citation | Yu XZ, et al. (2000) CD28-specific antibody prevents graft-versus-host disease in mice. J Immunol 164(9):4564-8 |
| abstractText | The costimulatory molecules B7-1 and B7-2 regulate T cell activation by delivering activation signals through CD28 and inhibitory signals through CTLA4. Graft-vs-host disease (GVHD) is caused by activated donor T cells. Previously, we showed that CD28-deficient donor T cells induced less-severe GVHD than wild-type donor T cells, suggesting that CD28 signals exacerbate GVHD. In this paper we demonstrate that CTLA4 signals attenuate the severity of GVHD. Targeting the CD28 receptor with a specific mAb modulates the receptor in vivo, inhibits donor T cell expansion, and prevents GVHD. CTLA4 signaling was necessary for this effect because treatment with a soluble ligand that blocks binding of B7 to both CD28 and CTLA4 did not prevent GVHD as effectively as anti-CD28 mAb. These results support the current model of T cell costimulation in which CD28 signals amplify GVHD while CTLA4 signals inhibit GVHD, providing evidence that selective targeting of CD28 might be a better therapeutic strategy for inducing immunological tolerance than blocking the ligands for both CD28 and CTLA4. |
