Alloantigen affinity and CD4 help determine severity of graft-versus-host disease mediated by CD8 donor T cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
Xue-Zhong YuClaudio Anasetti

Abstract

TCR affinity dictates T cell selection in the thymus and also has a high impact on the fate of peripheral T cells. Graft-vs-host disease (GVHD) is a pathological process initiated by activation of donor T cells after adoptive transfer into an allogeneic recipient. How TCR affinity affects the potential of alloreactive T cells to induce GVHD is unclear. Using alloreactive CD4+ and CD8+ TCR transgenic (Tg) T cells, GVHD models are presented that allow for the visualization of how CD8+ alloreactive T cells behave in response to alloantigens with different TCR affinity in the absence or presence of CD4 help. In a nonmyeloablative transplant model where GVHD lethality is due to marrow aplasia, alloreactive CD8+ TCR Tg T cells induced significantly more severe GVHD in the recipients that express an intermediate-affinity alloantigen than in the recipients that express a high-affinity alloantigen. In a myeloablative transplant model where GVHD lethality is due to epithelium injury, CD8+ TCR Tg cells were also more pathogenic in the recipients with an intermediate-affinity alloantigen than in those with a high-affinity alloantigen. The presence of alloreactive CD4+ TCR Tg cells enhanced the potential of CD8+ TCR Tg cells to cause GVHD i...Continue Reading

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Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xue-Zhong YuClaudio Anasetti

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Citations

Nov 13, 2009·The Journal of Clinical Investigation·Javier O ValenzuelaAmer A Beg
May 12, 2011·Disease Models & Mechanisms·Mark A Schroeder, John F DiPersio
Jul 29, 2009·European Journal of Immunology·Erick RiquelmeAlexis M Kalergis
May 4, 2016·Cellular and Molecular Life Sciences : CMLS·Barbara ÉrsekZoltán Pós
Nov 19, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jianing FuXue-Zhong Yu
Dec 17, 2020·Frontiers in Immunology·Mahinbanu MammadliMobin Karimi
Apr 15, 2021·IScience·Mahinbanu MammadliMobin Karimi

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