TY - JOUR
T1 - Hybrid antibody mediated veto of cytotoxic T lymphocyte responses
AU - Qi, Yan
AU - Berg, Rance
AU - Singleton, Michael A.
AU - Debrick, J. Eric
AU - Staerz, Uwe D.
PY - 1996/5/1
Y1 - 1996/5/1
N2 - Strategies are being sought that allow the induction of specific tolerance to allogeneic transplants without affecting other immune functions. The so- called veto effect has been described as one such technology where CD8+ cells suppress responses of class I MHC-restricted T-lymphocyte precursors to antigens expressed by those CD8+ veto cells. Yet, veto inhibition will not be able to provide complete tolerance to allogeneic grafts since it only operates on cell populations that express CD8. Other types of cells prevalent in most organs express different tissue-specific antigens that are recognized by alloreactive T-cells. Therefore, complete tolerance to an allogeneic transplant can only be achieved if all cellular components within the graft acquire the immune-inhibitory function. Here, we studied whether the veto effect could be exploited for this purpose nevertheless. We produced a hybrid antibody (HAb) combining a mAb specific for a class I MHC molecule with a soluble CD8 molecule. We found that this HAb specifically and effectively transferred veto inhibition to different stimulator cell populations. Thus, we have developed a strategy that promises to selectively and completely tolerize graft-specific CTLs without affecting normal immune responses.
AB - Strategies are being sought that allow the induction of specific tolerance to allogeneic transplants without affecting other immune functions. The so- called veto effect has been described as one such technology where CD8+ cells suppress responses of class I MHC-restricted T-lymphocyte precursors to antigens expressed by those CD8+ veto cells. Yet, veto inhibition will not be able to provide complete tolerance to allogeneic grafts since it only operates on cell populations that express CD8. Other types of cells prevalent in most organs express different tissue-specific antigens that are recognized by alloreactive T-cells. Therefore, complete tolerance to an allogeneic transplant can only be achieved if all cellular components within the graft acquire the immune-inhibitory function. Here, we studied whether the veto effect could be exploited for this purpose nevertheless. We produced a hybrid antibody (HAb) combining a mAb specific for a class I MHC molecule with a soluble CD8 molecule. We found that this HAb specifically and effectively transferred veto inhibition to different stimulator cell populations. Thus, we have developed a strategy that promises to selectively and completely tolerize graft-specific CTLs without affecting normal immune responses.
UR - http://www.scopus.com/inward/record.url?scp=0029980866&partnerID=8YFLogxK
U2 - 10.1084/jem.183.5.1973
DO - 10.1084/jem.183.5.1973
M3 - Article
C2 - 8642307
AN - SCOPUS:0029980866
SN - 0022-1007
VL - 183
SP - 1973
EP - 1980
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 5
ER -