CMV-Infected Kidney Grafts Drive the Expansion of Blood-Born CMV-Specific T-Cells Restricted by Shared HLA Molecules Through Presentation on Donor's Cells.

P. Gatault,^1,2 S. Al-Hajj,¹ J. Noble,^1,2 E. Chevallier,^1,2 M. Piollet,¹ C. Forconi,¹ R. Lemoine,¹ J.-M. Halimi,^1,2 M. Büchler,^1,2 C. Baron.^1,2

¹EA 4245, François-Rabelais University, Tours, France
²Kidney Transplantation Department, CHRU, Tours, France

Meeting: 2017 American Transplant Congress

Abstract number: 44

Keywords: Cytomeglovirus, Lymphocyte activation

Session Information

Session Name: Concurrent Session: Innate Pathways of Clinical Alloreactivity

Session Type: Concurrent Session

Date: Sunday, April 30, 2017

Session Time: 2:30pm-4:00pm

Presentation Time: 3:18pm-3:30pm

Location: E352

Background. Cytomegalovirus specific immune response is crucial to control CMV infection in kidney transplant recipients (KTR), in whom recipient CMV can reactivated (R+) and donor CMV superinfected (D+R+) or primary infected recipients (D+R-). Effect of CMV-superinfection by kidney graft on CMV-specific T cell response is not yet well defined and role of CMV infected donor cells in the development of CMV specific immune response remains poorly understood. Patient and methods. We assessed specific immune response using IFN-ɣ ELISOPT and pp65 dextramers in 115 KTR (D+R- 31, D+R+ 44, D-R+ 40). Results We observed that number of IFN-ɣ-producing cells was higher in D+R+ as compared to D-R+ recipients (3224 [850-9311] vs. 1983 [101-8785] spots/10⁶ CD3+ cells, p=0.004). Effect of superinfection remained in patients sharing at least one HLA-I identity (D+R+ 3245 [824-12999] vs. D-R+ 1791 [111-8614] spots/10⁶ CD3+ cells, p=0.003) but disappeared in full HLA-I mismatched KTR (D+R+ 2505 [1055-6818] vs. D-R+ 3651 [143-5961] spots/10⁶ of CD3+ cells, p=0.430). This results suggested that presentation of CMV peptides by donor cells was crucial to stimulate the expansion of pp65-specific memory CD8 T cells. Then, we compared in D+R- recipient number of anti CMVpp65 CD8+-T cells restricted by HLA-A2 depending on whether the donor expressed or not HLA-A2, to determine role of shared HLA-I and kidney allograft in CMV-specific CD8 T cell expansion. Patients who received non-HLA-A2 kidneys developed very few anti-CMVpp65 T-cells restricted by HLA-A2 as compared to those who received an HLA-A2 expressing kidney (300 [0-14638] vs 17,972 [222-85594] anti CMVpp65 CD8T-cells/10⁶ of CD8 cells, p=0.001). Conclusion. We bring for the first time valuable evidences that CMV-infected donor cells drives inflation of memory CMV specific CD8 T cells in kidney transplant recipients.

CITATION INFORMATION: Gatault P, Al-Hajj S, Noble J, Chevallier E, Piollet M, Forconi C, Lemoine R, Halimi J.-M, Büchler M, Baron C. CMV-Infected Kidney Grafts Drive the Expansion of Blood-Born CMV-Specific T-Cells Restricted by Shared HLA Molecules Through Presentation on Donor's Cells. Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Gatault P, Al-Hajj S, Noble J, Chevallier E, Piollet M, Forconi C, Lemoine R, Halimi J-M, Büchler M, Baron C. CMV-Infected Kidney Grafts Drive the Expansion of Blood-Born CMV-Specific T-Cells Restricted by Shared HLA Molecules Through Presentation on Donor's Cells. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/cmv-infected-kidney-grafts-drive-the-expansion-of-blood-born-cmv-specific-t-cells-restricted-by-shared-hla-molecules-through-presentation-on-donors-cells/. Accessed November 22, 2024.

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