William M. Baldwin, M.D., Ph.D.
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 445-2384
Fax: (216) 444-8372
Advances in immunosuppression have decreased the incidence of acute rejection, but the survival of all organ transplants continues to be limited by chronic rejection. Until recently, experimental models of transplantation have focused primarily on the T cell arm of adaptive immunity as the entire cause of acute and chronic rejection. Based on our knowledge of T cells, increasingly sophisticated immunosuppressive regimens have been designed. Unfortunately, the current immunosuppressive protocols are not effective in preventing antibody-mediated rejection. Antibody responses to transplants continue to present practical clinical problems because many patients have been exposed to histocompatibility antigens by previous blood transfusions, transplants or pregnancy. Previous exposure to alloantigens is one of the major differences between clinical patients and most experimental models of transplantation. Although rejection can result from pure antibody-mediated rejection, more frequently rejection is part of a comprehensive immune response that includes some degree of cellular rejection. Cellular and humoral immunity are highly interactive responses. The mechanisms underlying these interactions are incompletely understood. The goal of our studies is to understand the mechanisms through which antibodies alter lymphocyte responses at the level of endothelial cells, platelets and leukocytes. These mechanisms have general relevance to vascular pathology.
- Determine the effects of intermittent interactions of antibodies and complement on endothelial cells.
- Determine the mechanisms by which T cells promote antibody and complement interactions with endothelial cells resulting in activatation and release of cytokines.
- Determine the mechanisms by which complement interactions with endothelial cells stimulate memory B cells resulting in local antibody production.
- Modulation of T cell and B cell interactions with vascular endothelial cells by antibodies, complement, and platelets
- Danturti S, Keslar KS, Steinhoff LR, Fan R, Dvorina N, Valujskikh A, Fairchild RL, Baldwin WM III. CD4+ T lymphocytes produce adiponectin in response to transplants. JCI Insight. 2017;2(12)e89641.
- Berger M, Baldwin WM III, Jordan SC. Potential roles for C1 inhibitor in transplantation. Transplantation 7: 1415-24, 2016.
- Kuo H-H, Fan R, Dvorina N, Chiesa-Vottero A, Baldwin WM III. Platelets in early antibody -mediated rejection of renal transplants. JASN 26(4):855-63, 2015. PMC4378099
- Kaul AMK, Goparaju S, Dvorina N, Iida S, Keslar KS, de la Motte CA Valujskikh A, Fairchild RL, Baldwin WM III. Acute and Chronic Rejection: Compartmentalization and Kinetics of Counterbalancing Signals in Cardiac Transplants. Am J Transplant 15(2):333-45, 2015. PMC4304877
- Baldwin WM III, Su CA, Shroka TM, Fairchild RL. Experimental Models of Cardiac Transplantation - design determines relevance. Curr Opin Organ Transplant. 19(5):525-30, 2014.
- Kuo HH, Morrell CN, Baldwin WM III. Alloantibody induced platelet responses in transplants: Potent mediators in small packages. Human Immunol. 73: 1233–38, 2012.
- Morrell CN, Murata K, Swaim AM, Mason E, Martin TV, Ballard M, Fox-Talbot K, Waswoska B, Baldwin WM III . In vivo platelet-endothelial cell interactions in response to MHC alloantibody. Circ Res.102:777-85, 2008.
- Kirk AD, Morrell CN, Baldwin WM III . Platelets influence vascularized organ transplants from start to finish Am J Transplant. 2008.
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