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A New Approach to the Blocking of Alloreactive T Cell-Mediated Graft-Versus-Host Disease by in Vivo Administration of anti-CXCR3 Neutralizing Antibody

A New Approach to the Blocking of Alloreactive T Cell-Mediated Graft-Versus-Host Disease by in Vivo Administration of anti-CXCR3 Neutralizing Antibody

Shan He, Qi Cao, Yuhua Qiu, Jianqing Mi, Jingwu Z Zhang, Min Jin, Hailiang Ge, Stephen G Emerson, Yi Zhang, Yanyun Zhang

J Immunol. 2008 Dec 1;181(11):7581-92.

PMID: 19017947

Abstract:

Chemokines and chemokine receptors play critical roles in directing the migration of alloreactive donor T cells into graft-vs-host disease (GVHD) target organs. However, blockade of GVHD by antagonist Ab against chemokine receptors remains an elusive goal. Using a mouse model of human GVHD, we demonstrate that in vivo administration of anti-CXCR3 Ab for 21 days (long-term), but not for 7 days (short-term), inhibits alloreactive CD8(+) T cell-mediated GVHD. During a graft-vs-host reaction, infused donor CD8(+) T cells generate two subsets of potent inducers of GVHD: CXCR3(+)CD8(+) and CXCR3(-)CD8(+) T cells. Compared with CXCR3(+)CD8(+) T cells, CXCR3(-)CD8(+) T cells produce less granzyme B, Fas ligand, IFN-gamma, and TNF-alpha. Interestingly, stimulation with either dendritic cells or IL-2 induces a dynamic conversion between CXCR3(+)CD8(+) and CXCR3(-)CD8(+) T cells. Short-term anti-CXCR3 Ab treatment inhibits only CXCR3(+)CD8(+) T cell-mediated GVHD, but not the disease induced by CXCR3(-)CD8(+) T cells. Prolonged in vivo administration of anti-CXCR3 Ab significantly reduces the infiltration of alloreactive CD8(+) T cells into GVHD target organs and inhibits GVHD mediated by either CXCR3(+)CD8(+) or CXCR3(-)CD8(+) T cells. Thus, we have established a novel and effective approach with the potential to give rise to new clinical methods for preventing and treating GVHD after allogeneic hematopoietic stem cell transplantation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413069	Monoclonal Anti-CXCR3 antibody produced in mouse			Price

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