Experimental Islet Transplantation

1. Experimental Islet Transplantation in NOD Mice. Dr. Auchincloss is studying the role of recurrent autoimmunity in the rejection of allogeneic islet transplants by diabetic NOD mice. In addition, these experiments have led to additional studies regarding the unusual rejection mechanisms used by NOD mice and their resistance to tolerance induction even for non-islet tissue transplants. These studies are being performed in collaboration with Drs. Vijay Kuchroo, Mohamed Sayegh, Christophe Benoist, and Diane Mathis.

2. Experimental Islet Transplantation in Monkeys.  Dr. Auchincloss and Dr. Maria Koulmanda are collaborating with Drs. A. Benedict Cosimi, Dicken Ko, and others to test potential strategies in monkeys for inducing tolerance to allogeneic islet transplants. Over fifty islet transplants have been performed using costimulatory blockade and mixed chimerism approaches. These studies also involve numerous other investigators including Drs. Terry Strom, R. Neal Smith, Dennis Sgroi, and others who use the tissues and blood samples from these experiments for analysis of gene expression and immunopathology.

3. The JDF Center for Islet Transplantation at Harvard Medical School. In addition to the above projects in which Dr. Auchincloss is directly involved, he is also responsible for organizing the work of the JDF Center for Islet Transplantation at Harvard Medical School. This Center involves over forty investigators at Harvard Medical School who are committed to working on strategies to achieve islet replacement therapy for children with diabetes without the need for long-term immunosuppression.

References:

1.      Auchincloss H Jr. In search of the elusive Holy Grail: the mechanisms and prospects for achieving clinical transplantation tolerance. A minireview. Amer. J. Transplant. 2001;1:6-12.

2.      Abdi R, Smith RN, Makhlouf L, Najafian N, Luster AD, Auchincloss H Jr, Sayegh MH. The role of the chemokine receptor 5 (CCR5) in islet allograft rejection. Diabetes 2002:51;2489-2495.

3.      Makhlouf L, Kishimoto K, Smith RN, Abdi R, Koulmanda M, Winn HJ, Auchincloss H Jr, Sayegh MH. The role of autoimmunity in islet allograft destruction: Major histocompatibility complex class II matching is necessary for autoimmune destruction of allogeneic islet transplants after T-cell costimulatory blockade. Diabetes 2002:51;3202-3210.

4.      Koulmanda M, Qipo A, Smith RN, Auchincloss H Jr. Pig islet xenografts are resistant to autoimmune destruction by non-obese diabetic recipients after anti-CD4 treatment. Xenotransplantation 2002;9:1-7.

5.      Koulmanda M, Qipo A, Chebrolu S, Auchincloss H Jr, Smith RN. The effect of low versus high dose of Streptozotocin in cynomolgus monkeys (macaca fascilularis). Amer. J. Transplant. 2003;3:267-72.

6.   Auchincloss H Jr., Sykes M, Sachs DH. Transplantation Immunology. In: Paul, W.E. ed. Fundamental Immunology. Chapter 46. Fifth Edition, New York: Lippincott-Raven Publishers. In press. 2003.

7.   Makhlouf L, Grey ST, Dong V, Csizmadia E, Arvelo MB, Auchincloss H Jr, Ferran C, Sayegh MH. Depleting anti-CD4 monoclonal antibody cures new-onset diabetes, prevents recurrent autoimmune diabetes, and delays allograft rejection in nonobese diabetic mice. Transplantation. 2004;77:990-7