HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, X.-Z. Articles by Anasetti, C. Search for Related Content PubMed PubMed Citation Articles by Yu, X.-Z. Articles by Anasetti, C.

Alloantigen Affinity and CD4 Help Determine Severity of Graft-versus-Host Disease Mediated by CD8 Donor T Cells¹

Xue-Zhong Yu^2,*,, Michael H. Albert^3,* and Claudio Anasetti^4,*,

^* Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and Department of Medicine, University of Washington, Seattle, WA 98195

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 in recipients with an intermediate-, but not with a high-, affinity alloantigen. These findings underscore that alloantigen affinity and CD4 help control the fate and pathogenicity of alloreactive CD8⁺ T cells in vivo.

This article has been cited by other articles:

				Y. Liang, C. Liu, J. Y. Djeu, B. Zhong, T. Peters, K. Scharffetter-Kochanek, C. Anasetti, and X.-Z. Yu 2 integrins separate graft-versus-host disease and graft-versus-leukemia effects Blood, January 15, 2008; 111(2): 954 - 962. [Abstract] [Full Text] [PDF]