CXCR5/CXCL13 interaction is important for double-negative regulatory T cell homing to cardiac allografts

The Journal of Immunology : Official Journal of the American Association of Immunologists
Boris P-L LeeLi Zhang

Abstract

Accumulating evidence indicates that regulatory T (Treg) cells control development of various diseases both systemically and locally. However, molecular mechanisms involved in Treg cell homing remain elusive. We have shown previously that alphabetaTCR(+)CD3(+)CD4(-)CD8(-) double-negative (DN) Treg cells selectively accumulate in tolerant allografts to maintain localized immune regulation. However, the molecular mechanism leading to the accumulation of DN Treg cells in tolerant grafts was not known. Our cDNA microarray analysis revealed significant up-regulation of chemokine receptor CXCR5 mRNA in DN Treg clones compared with nonregulatory clones. In this study, we examined the importance of CXCR5 in mediating DN Treg migration. Compared with CD4 and CD8 T cells, both primary DN Treg cells and clones constitutively express high levels of CXCR5 protein, enabling them to migrate toward increasing CXCL13 gradients in vitro. After infusion into recipient mice, CXCR5(+) DN Treg clones, but not their CXCR5(-) mutants, preferentially accumulated in cardiac allografts and could prevent graft rejection. Furthermore, we found that allogeneic cardiac allografts express high levels of CXCL13 mRNA compared with either recipient native hearts...Continue Reading

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Citations

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