Robert Fairchild Laboratory

Research

Epidermal application of reactive haptens such as urushiol, the reactive agent in poison ivy, and subsequent challenge results in the development of a T cell mediated inflammatory response termed allergic contact dermatitis or contact hypersensitivity (CHS). Using several different strategies we have observed that hapten application primes two reactive T cell populations: IFN-g producing CD8+ T cells which are the effector T cells of the response and CD4+ T cells producing IL-4, IL-5 and IL-10 which regulate the magnitude and duration of the CHS response. Once primed, recruitment of the CD4+ and CD8+ T cells to tissue challenge sites requires a complex cascade of chemokine production and leukocyte infiltration. This cascade is initiated when hapten induces keratinocytes to produce chemoattractants such as Groa which recruit neutrophils to the challenge site. The goal of our studies is to define the neutrophil derived products and/or activities which lead to the recruitment of the hapten-primed T cells to the site and the effector functions expressed by the T cells following activation by the hapten at the site to elicit the CHS response.

Selected Publications

1. Kish DD, Volokh N, Baldwin WM 3rd and Fairchild RL: Hapten application to the skin induces an inflammatory program directing hapten-primed effector CD8 T cell interaction with hapten-presenting endothelial cells. J. Immunol. 186: 2117-2126, 2011.
2. Setoguchi K, Schenk AD, Ishii D, Hattori Y, Baldwin WM 3rd, Tanabe K and Fairchild RL: LFA-1 antagonism inhibits early infiltration of endogenous memory CD8 T cell into cardiac allografts and donor-reactive T cell priming. Am. J. Transplant. 11:923-935, 2011.
3. Ishii D, Schenk AD, Baba S and Fairchild RL: Role of TNFa in early chemokine production and leukocyte infiltration into heart allografts. Am. J. Transplant. 10:59-68, 2010.
4. Rosenblum JM, Shimoda N, Schenk AD, Zhang H, Kish DD, Keslar K, Farber JM, and Fairchild RL: CXCL9 and CXCL10 are antagonistic costimulation molecules during the priming of alloreactive T cell effectors. J. Immunol. 184:3450-3460, 2010.
5. Danzinger-Isakov L, Cherkassky L, Siegel H, McManamon M, Kramer K, Budev M, Sawinski D, Augustine JJ, Hricik DE, Fairchild R, Heeger PS and Poggio ED: Effects of influenza immunization on humoral and cellular alloreactivity in humans. Transplantation 89:838-844, 2010.
6. Mannon RB and Fairchild RL: Allograft fibrosis-unmasking the players at the dance. Am. J. Transplant. 10:201-202, 2010.
7. Valujskikh A, Baldwin WM 3rd and Fairchild RL: Recent progress and new perspectives in studying T-cell responses to allografts. Am. J. Transplant. 10:1135-1142, 2010.
8. Baldwin WM 3rd, Valujskikh A and Fairchild RL: Antibody-mediated rejection: emergence of animal models to answer clinical questions. Am. J. Transplant. 10:1117-1125, 2010.
9. Gorbachev AV and Fairchild RL: CD4+CD25+ regulatory T cells utilize FasL as a mechanism to restrict DC priming functions in cutaneous immune responses. Eur. J. Immunol. 40:2006-2015, 2010.
10. Schenk AD, Gorbacheva V, Rabant M, Fairchild RL and Valujskikh A: Effector functions of donor-reactive CD8 memory T cells are dependent on ICOS induced during division in cardiac grafts. Am. J. Transplant. 9:64-69, 2009.
11. Rosenblum JM, Zhang Q-W, Siu G, Collins TL, Sullivan T, Medina J and Fairchild RL: CXCR3 antagonism impairs the development of donor-reactive, IFN-g producing effectors and prolongs allograft survival. Transplantation 87:360-369, 2009.
12. Neznanov N, Gorbachev AV, Neznanova L, Komarov AP, Gurova KV, Gasparian AV, Banerjee AK, Almasan A, Fairchild RL and Gudkov AV: Anti-malaria drug blocks proteotoxic stress response: anti-cancer implications. Cell Cycle 8:3960-3970, 2009.
13. Kish DD, Li X and Fairchild RL: CD8 T cells producing IL-17 and IFN-g initiate the innate immune response required for responses to antigen skin challenge. J. Immunol. 82:5949-5959, 2009.
14. Auerbach MB, Shimoda N, Amano H, Kish DD, Farber JM and Fairchild RL: Monokine induced by IFN-g (MIG/CXCL9) is derived from both donor and recipient sources during rejection of class II MHC disparate skin allografts. Am. J. Pathol. 174:2172-2181, 2009.
15. Nozaki T, Rosenblum JM, Schenk AD, Ishii D and Fairchild RL: CCR5 is required for regulation of alloreactive T cell responses to single class II MHC-mismatched murine cardiac grafts. Am. J. Transplant. 9:2251-2261, 2009.
16. Fukuzawa N, Schenk AD, Petro M, Baldwin WM, III, Nonomura K, and Fairchild RL: High renal ischemia temperature increases neutrophil chemoattractant production and tissue injury during reperfusion without an identifiable role for CD4 T cells in the injury. Transplant Immunol. 22:62-71, 2009.
17. Poggio ED and Fairchild RL: Breaking down donor-reactive T-cell activation to two steps. Am. J. Transplant. 9:2651-2652, 2009.
18. Wehner JR, Morrell CN, Rodriguez ER, Fairchild RL and Baldwin WM 3rd: Immunological challenges of cardiac transplantation: the need for better animal models to answer current clinical questions. J. Clin. Immunol. 29:722-729, 2009.
19. Bickerstaff A, Nozaki T, Wang J-J, Pelletier R, Nadasdy G, Nadasdy T and Fairchild RL: Acute humoral rejection of renal allografts in CCR5-/- recipients recapitulates clinical histopathology. Am. J. Transplant. 8:557-566, 2008.
20. Schenk AD, Nozaki T, Rabant M, Valujskikh A and Fairchild RL: Donor-reactive CD8 memory T cells infiltrate cardiac allografts within 24 hours post-transplant in naïve recipients. Am. J. Transplant. 2008; 8: 1652–1661.
21. Nozaki T, Rosenblum JD, Ishii D, Tanabe K and Fairchild RL: CD4 T cell mediated rejection of cardiac allografts in B cell deficient mice. J. Immunol. 181: 5257-5263, 2008.
22. Halloran PF and Fairchild RL: The puzzling role of CXCR3 and its ligands in organ allograft rejection. Am. J. Transplant. 8:1578-1579, 2008.
23. Schenk AD, Rosenblum JD and Fairchild RL: Chemokine directed strategies to attenuate allograft rejection. Clin. Lab. Med. 28: 441-454, 2008.