31 Dec Improving Suceess of Corneal Transplantation
MedicalResearch.com Interview with:
Dr. Jerry Y. Niederkorn, Ph.D.
George A. and Nancy P. Shutt
Professorship in Medical Sciences
Royal C. Miller Chair in Age-Related Macular Degeneration Research Professor of Ophthalmology and Microbiology
Vice Chair, Research (Department of Ophthalmology)
Department of Ophthalmology, University of Texas Southwestern Medical Center
Dallas, TX
FN-γ Blocks CD4+CD25+ Tregs and Abolishes Immune Privilege of Minor Histocompatibility Mismatched Corneal Allografts
MedicalResearch.com: What are the main findings of the study?
Dr. Niederkorn: These findings indicate that a combination of two simple maneuvers increases the acceptance of corneal transplants. In the past, there was no clear benefit in performing tissue matching of the cornea donor’s major histocompatibility complex (MHC) with the recipient of the corneal transplant. However, our study in experimental animals revealed that blocking a single immune system molecule called interferon-gamma (IFN-γ) combined with matching the corneal transplant donor with the transplant recipient’s MHC gene complex reduced the risk of rejection to less than 10% in the total absence of anti-rejection drugs. This study revealed that blocking this single immune system molecule promoted the development of immune system cells called T regulatory cells (Tregs) that suppressed the lymphocytes that are responsible for attacking organ transplants.
MedicalResearch.com: Were any of the findings unexpected?
Dr. Niederkorn: Two aspects of this study were especially unexpected.
First, the prevailing theory in in the field of transplantation immunology has assumed that a key immune system molecule called IFN-γ was necessary for and facilitated the immune rejection of organ transplants. Our study showed that blocking this molecule (IFN-γ) in recipients of corneal transplants in which tissue typing for the MHC compatibility was performed resulted in an exacerbation, rather than a prevention of corneal graft rejection.
The second unexpected finding was that tissue matching of the MHC of the cornea donor and the corneal graft recipient did not enhance graft survival. However, MHC matching and blocking IFN-γ with a monoclonal antibody prevented graft rejection.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Niederkorn: Matching the corneal transplant donor and the graft recipient alone offers no benefit for long-term corneal graft survival. In the absence of MHC tissue matching, blocking IFN-γ alone not only fails to enhance graft survival, but in fact exacerbates immune rejection. However, the combination of the two maneuvers guarantees corneal graft acceptance in rodents. It remains to be determined if the same condition occurs in patients, especially “high risk” transplant recipients who have rejected a previous corneal transplant.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Niederkorn: It will be important to determine if a blocking antibody against IFN-γ can be administered in eye drops as a simple application that has minimal systemic effects.
There is evidence that the immune systems of hosts with long-term surviving corneal transplants become “tolerant” of the foreign histocompatibility molecules on the transplant and remain in a dormant or quiescent state. Therefore, it will useful to ascertain if the immune systems of hosts who have received MHC-matched corneal grafts and have been treated with anti-IFN-γ antibody become reprogrammed and as a result, the administration of antibodies against IFN-γ can be tapered and eventually terminated.
Citation:
Last Updated on April 10, 2015 by Marie Benz MD FAAD