Alloreactive CD154-expressing T-cell subsets with differential sensitivity to the immunosuppressant, belatacept: potential targets of novel belatacept-based regimens

Scientific Reports

Volumn 5, Issue 1, 2015, Pages

  Ashokkumar, Chethan ^a,c   Ganguly, Bishu ^b   Townsend, Robert ^b   White, Jaimie ^a   Levy, Samantha ^a   Moritz, Michael ^c   Mazariegos, George ^c   Sun, Qing ^c   Sindhi, Rakesh ^c  

^a A Subsidiary of Neurolign Technologies Inc   (United States)

^b BRISTOL MYERS SQUIBB   (United States)

^c UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABATACEPT; CD28 ANTIGEN; CD40 LIGAND; IMMUNOSUPPRESSIVE AGENT;

CLUSTER ANALYSIS; CYTOLOGY; DRUG EFFECTS; GRAFT REJECTION; HUMAN; IMMUNOLOGY; KIDNEY TRANSPLANTATION; METABOLISM; MONONUCLEAR CELL; T LYMPHOCYTE SUBPOPULATION;

ABATACEPT; ANTIGENS, CD28; CD40 LIGAND; CLUSTER ANALYSIS; GRAFT REJECTION; HUMANS; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANTATION; LEUKOCYTES, MONONUCLEAR; T-LYMPHOCYTE SUBSETS;

EID: 85021389136     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/SREP15218     Document Type: Article

References (24)

1. Vincenti, F. et al. A Phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT Study). Am. J. Transplant. 10, 535–546 (2010).
2. Larsen, C. P. et al. Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am. J. Transplant. 5, 443–453 (2005).
3. Behar, S. M., Porcelli, S. A., Beckman, E. M. & Brenner, M. B. A pathway of costimulation that prevents anergy in CD28-T-cells: B7-independent costimulation of CD1-restricted T cells. J. Exp. Med. 182, 2007–2018(1995).
4. Croft, M., Bradley, L. M. & Swain, S. L. Naive versus memory CD4 T cell response to antigen. Memory cells are less dependent on accessory cell costimulation and can respond to many antigen-presenting cell types including resting B cells. J. Immunol. 152, 2675–2685 (1994).
5. Lo, D. J. et al. Selective targeting of human alloresponsive CD8+ effector memory T cells based on CD2 expression. Am. J. Transplant. 11, 22–33 (2011).
6. Sindhi, R. et al. Enhanced donor-specific alloreactivity occurs independently of immunosuppression in children with early liver rejection. Am J Transplant. 5, 96–102 (2005).
7. Ashokkumar, C. et al. Allospecific CD154+ T cells associate with rejection risk after pediatric liver transplantation. Am. J. Transplant. 9, 179–191 (2009).
8. Ashokkumar, C. et al. Allospecific CD154+ T cells identify rejection-prone recipients after pediatric small-bowel transplantation. Surgery 146, 166–173 (2009).
9. Ashokkumar, C. et al. Allospecific CD154+ T-cytotoxic memory cells identify recipients experiencing acute cellular rejection after renal transplantation. Transplantation 92, 433–438 (2011).
10. Sindhi, R. et al. Allospecific CD154T-cytotoxic memory cells as potential surrogate for rejection risk in pediatric intestine transplantation. Pediatr. Transplant. 16, 83–91 (2012).
11. Ashokkumar, C. et al. Proliferative alloresponse of T cytotoxic cells identifies rejection-prone children with small bowel transplantation. Transplantation 89, 1371–1377 (2010).
12. International Panel: Demetris, A. J., Batts, K. P., Dhillon, A. P. et al. Banff schema for grading liver allograft rejection: An international consensus document. Hepatology. 25(3), 658–663 (1997).
13. Sindhi, R. et al. Stimulated response of peripheral lymphocytes may distinguish cyclosporine effect in renal transplant recipients receiving a cyclosporine+ rapamycin regimen. Transplantation 69, 432–436 (2000).
14. Sindhi, R. et al. Modeling individual variation in biomarker response to combination immunosuppression with stimulated lymphocyte responses-potential clinical implications. J. Immunol. Methods 272, 257–272 (2003).
15. Merion, R. M. et al. Partial T-cell activation and anergy induction by polyclonal antithymocyte globulin. Transplantation. 65(11), 1481–1489 (1998).
16. Shino, M. Y. Usefulness of immune monitoring in lung transplantation using adenosine triphosphate production in activated lymphocytes. J Heart Lung Transplant. 9, 996–1002 (2012).
17. Talukdar, A. et al. Lymphocyte subset reconstitution in pediatric liver recipients induced with steroid-free rabbit anti-human thymocyte globulin. Pediatr. Transplant. 12, 804–808 (2008).
18. Talukdar, A. et al. Lymphocyte subset reconstitution patterns in children with small bowel transplantation induced with steroid-free rabbit anti-human thymocyte globulin. Pediatr. Transplant. 13, 353–359 (2009).
19. Wood, K. J. & Sakaguchi, S. Regulatory T cells in transplantation tolerance. Nat. Rev. Immunol. 3, 199–210 (2003).
20. Zhai, Y., Meng, L., Gao, F., Busuttil, R. W. & Kupiec-Weglinski, J. W. Allograft rejection by primed/memory CD8+ T cells is CD154 blockade resistant: therapeutic implications for sensitized transplant recipients. J. Immunol. 169, 4667–4673 (2002).
21. Gao, D., Li, J., Orosz, C. G. & Bumgardner, G. L: Different costimulation signals used by CD4(+ ) and CD8(+ ) cells that independently initiate rejection of allogenic hepatocytes in mice Hepatology 32, 1018–1028 (2000).
22. Koyama, I. et al. Depletion of CD8 memory T cells for induction of tolerance of a previously transplanted kidney allograft. Am. J. Transplant. 5, 1055–1061 (2007).
23. Traitanon, O. et al. IL-15 induces alloreactive CD28(-) memory CD8 T cell proliferation and CTLA4-Ig resistant memory CD8 T cell activation. Am. J. Transplant. 14, 1277–1289 (2014).
24. Ashokkumar, C. et al. Antithymocyte globulin facilitates alloreactive T-cell apoptosis by means of caspase-3: potential implications for monitoring rejection-free outcomes. Transplantation 99, 164–170 (2015).