The Bumgardner Lab recently submitted the article Invariant NKT cells promote the development of highly cytotoxic multipotent CXCR3+CCR4+CD8+ T cells that mediate rapid hepatocyte allograft rejection, the article has been selected by Editors as a Top Read for the December 15, 2022, issue of the Journal of Immunology. Publication details to follow.
Jason M. Zimmerer, Bryce A. Ringwald, Sachi R. Chaudhari, Jing Han, Chelsea M. Peterson, Robert T Warren, Madison M. Hart, Mahmoud Abdel-Rasoul, Ginny L. Bumgardner. “Invariant NKT cells promote the development of highly cytotoxic multipotent CXCR3+CCR4+CD8+ T cells that mediate rapid hepatocyte allograft rejection”. Journal of Immunology, Accepted Oct. 2021
Surgeon scientists bring to bear highly specialized talent and innovative and impactful solutions for complicated clinical problems. Our objective is to inform and provide framework for early stage surgeon scientist training and support.
Barker JC, Jalilvand A, Onuma A, Shelby R, Shah K, Daulton R, Bumgardner GL. Facilitating Success of the Early Stage Surgeon-Scientist Trainee: Growing the Surgeon Scientist Pipeline. Ann Surg. 2021 Apr 30. doi: 10.1097/SLA.0000000000004924. Epub ahead of print. PMID: 33938494.
Humoral Alloimmunity. As the transplant community became aware of the detrimental effects of humoral alloimmunity on allograft function and survival, my lab began to investigate immunoregulatory mechanisms impacting de novo alloantibody production and mechanisms of alloantibody mediated injury in our experimental models. This is now a major focus of my laboratory to better understand the regulation and impact of humoral alloimmunity after transplantation.
- Horne PH , Zimmerer JM, Fisher M, Lunsford KE, Nadasdy G, Nadasdy T, Van Rooijen N, Bumgardner, GL. Critical Role of Effector Macrophages in Mediating CD4-Dependent Alloimmune Injury of Transplanted Liver Parenchymal Cells. J Immunology, 2008, 181:1224-1231. PMC3022512
- Zimmerer JM, Pham TA, Sanders VM, Bumgardner GL. CD8+ T cells negatively regulate IL-4-dependent, IgG1‑dominant post‑transplant alloantibody production. Journal of Immunology, 2010 Dec 15; 185(2): 7285-92. PMC3010751
- Zimmerer, J.M., Pham, T.A., Wright, C.L., Tobin, K.J., Sanghavi, P.B., Elzein, S.M., Sanders, V.M., Bumgardner, G.L. Alloprimed CD8+ T cells Regulate Alloantibody and Eliminate Alloprimed B cells Through Perforin- and FasL-dependent Mechanisms. AJT 14(2): 295-304, 2014 PMC4018729
- Zimmer J.M., Liu X.L., Blaszcak A, Avila C.L., Pham T.A., Warren R.T., Bumgardner G.L. Critical Role of macrophage FcγR signaling and ROS in alloantibody-mediated hepatocyte rejection. Journal of Immunology, 2018 Dec;201(12):3731-3740. PMCID: PMC6289737.f) Zimmerer, J.M., Ringwald, B.A., Elzein, S.M., Avila, C.L., Warren, R.T., Abdel-Rasoul, M., Bumgardner, G.L. Antibody-suppressor CD8+ T cells require CXCR5. Transplantation. Transplantation. 2019 Sep;103(9):1809-1820. PMID:30397035
Cellular Alloimmunity. Early immunosuppression strategies were CD4+ T cell centric and focused on regulation of alloreactive CD4+ T cell responses. Even though it was recognized that alloreactive CD8+ cytolytic T cells could mediate allograft damage, the rationale to develop immunotherapeutic agents targeting CD4+ T cells was based on the concept that maturation of CD8 effector cells was exclusively CD4-dependent. My lab was among the first to publish studies showing the importance of CD4-independent CD8+ T cell alloimmune responses mediating rejection through pathways that were resistant to conventional immunotherapy. This discovery led to a series of studies to better understand this unconventional rejection pathway. We reported the unique TNF-a dependent (perforin- and FasL-independent) effector function of these cytolytic CD8+ T cells and the efficacy of dual therapy targeting LFA-1 and CD40L costimulation for longterm suppression of alloreactive CD4-independent CD8+ T cell mediated rejection.
- Wang Y, Gao D, Lunsford KE, Frankel WL, Bumgardner GL. Targeting LFA-1 synergizes with CD40/CD40L costimulation blockade for suppression of both CD4-dependent and CD8-dependent rejection. American Journal of Transplantation 2003;3(10):1251-8.
- Lunsford KE, Koester MA, Eiring AM, Gao D, Horne PH, and Bumgardner GL. Targeting LFA-1 and CD154 suppresses the in vivo activation and cytolytic development of (CD4-independent) CD8+ T cells. Journal of Immunology, 2005: 175(12); 7855-66.
- Lunsford KE, Horne PH, Koester MA, Eiring AM, Walker JP, Bumgardner GL. Activation and Maturation of Alloreactive CD4-independent, CD8+ Cytolytic T Cells. American Journal of Transplantation 2006: 6(10); 2268-2281.
- Zimmerer, J.M., Horne, P.H., Fiessinger, L.A., Fisher, M.G., Pham, T.A., Saklayen, S.L., and Bumgardner GL. Cytotoxic Effector Function of CD4-Independent, CD8+ T Cells Is Mediated by TNF-α/TNFR. Transplantation. 2012 Dec 15; 94(11):1103-10, 2012. PMCID: PMC3522862.
Allograft Immunogenicity. My lab is one of the first to introduce the concept that both tissue specific factors and the immune microenvironment significantly influence subsequent alloimmune responses. Using MHC-matched cell transplant models we reported differential patterns of alloimmunity for hepatocellular and islet transplants transplanted to different immune locales. We also published that MHC-matched heart and hepatocyte allografts transplanted concurrently to the same host evoked disparate immune responses and transplant outcomes. These and many studies by others have established the complexity of allograft immunogenicity in initiating alloimmunity and autoimmunity which can be detrimental to allograft function and survival.
- Bumgardner GL, Gao D, Li J, Bickerstaff A, Orosz CG. MHC-identical heart and hepatocyte allografts in mice evoke disparate immune responses within the same host. Transplantation 74(6):855-64, 2002.
- Lunsford KE, Gao D, Eiring AM, Frankel WL, and Bumgardner GL. Evidence for tissue directed immune responses: Analysis of CD4-dependent and CD8-dependent alloimmunity. Transplantation 2004, 78(8): 1125-33.
- Horne PH, Lunsford KE, Walker JP, Koester MA, and Bumgardner GL. Recipient immune repertoire and engraftment site influence the immune pathway effecting acute hepatocellular allograft rejection. Cell Transplantation, 2008 July 15; 17(7): 829-844.
- Zimmerer J.M, Horne P.H., Fisher M.G., Pham T.A., Lunsford K.E., Ringwald B.A., Avila C.L., Bumgardner G.L. Unique CD8+ T cell Responses Primed in the Liver. 2016 Transplantation, Sep; 100(9): 1907-15. PMC493592
Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/sites/myncbi/ginny.bumgardner.1/bibliography/40712617/public/?sort=date&direction=descending