Allografts Stimulate Cross-reactive Virus-specific Memory CD8 T Cells with Private Specificity

Overview

Journal Am J Transplant

Publisher Elsevier

Specialty General Surgery

Date 2010 Jul 28

PMID 20659086

Citations 22

Authors

M A Brehm

K A Daniels

B Priyadharshini

T B Thornley

D L Greiner

A A Rossini

R M Welsh

Affiliations

Soon will be listed here.

Abstract

Viral infections have been associated with the rejection of transplanted allografts in humans and mice, and the induction of tolerance to allogeneic tissues in mice is abrogated by an ongoing viral infection and inhibited in virus-immune mice. One proposed mechanism for this 'heterologous immunity' is the induction of alloreactive T cell responses that cross-react with virus-derived antigens. These cross-reactive CD8 T cells are generated during acute viral infection and survive into memory, but their ability to partake in the immune response to allografts in vivo is not known. We show here that cross-reactive, virus-specific memory CD8 T cells from mice infected with LCMV proliferated in response to allografts. CD8 T cells specific to several LCMV epitopes proliferated in response to alloantigens, with the magnitude and hierarchy of epitope-specific responses varying with the private specificities of the host memory T cell repertoire, as shown by adoptive transfer studies. Last, we show that purified LCMV-specific CD8 T cells rejected skin allografts in SCID mice. These findings therefore implicate a potential role for heterologous immunity in virus-induced allograft rejection.

Citing Articles

Posttransplant complications: molecular mechanisms and therapeutic interventions.

Liu X, Shen J, Yan H, Hu J, Liao G, Liu D MedComm (2020). 2024; 5(9):e669.

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Single-cell transcriptomic analysis of renal allograft rejection reveals insights into intragraft TCR clonality.

Shi T, Burg A, Caldwell J, Roskin K, Castro-Rojas C, Chukwuma P J Clin Invest. 2023; 133(14).

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Heterologous Immunity of Virus-Specific T Cells Leading to Alloreactivity: Possible Implications for Solid Organ Transplantation.

Karahan G, Claas F, Heidt S Viruses. 2021; 13(12).

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CMV Status Drives Distinct Trajectories of CD4+ T Cell Differentiation.

Zhang W, Morris A, Peek E, Karadkhele G, Robertson J, Kissick H Front Immunol. 2021; 12:620386.

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Impact of infection on transplantation tolerance.

Yu S, Su C, Luo X Immunol Rev. 2019; 292(1):243-263.

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