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Originally published online as doi:10.1189/jlb.0205078 on July 6, 2005

Published online before print July 6, 2005
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(Journal of Leukocyte Biology. 2005;78:595-604.)
© 2005 by Society for Leukocyte Biology

Recombinant dimeric MHC antigens protect cardiac allografts from rejection and visualize alloreactive T cells

Ari Fried*, Martina Berg*, Bhavna Sharma{dagger}, Sabrina Bonde* and Nicholas Zavazava*,{ddagger},1

* University of Iowa Hospitals and Clinics & VAMC Iowa City, Department of Internal Medicine;
{dagger} Gemini Sciences Inc., San Diego, California; and
{ddagger} Immunology Graduate Program, University of Iowa, Iowa City

1Correspondence: University of Iowa Hospitals and Clinics, C51-F, Department of Internal Medicine, 200 Hawkins Dr., Iowa City, IA 52242. E-mail: nicholas-zavazava{at}uiowa.edu

Monomeric and dimeric soluble major histocompatibility complex (MHC) molecules down-regulate activated T cells in an antigen-specific manner in vitro. This property could be exploited to modulate alloresponses in vivo but has remained difficult to demonstrate. Here, intraperitoneal infusion of a Lewis-derived rat MHC class I molecule, RT1.Al-Fc, in Dark Agouti (RT1.Aa) recipient rats prolonged cardiac graft survival, which led to permanent engraftment. This effect was mediated by T cell impairment of target cell lysis by CD8+ T cells and down-regulation of interferon-{gamma} production by CD4+ T cells. The binding of the dimeric MHC allowed ex vivo visualization of alloreactive T cells in peripheral blood, splenocytes, and allografts, revealing low frequency of alloreactive CD8+ T cells after establishment of permanent engraftment of cardiac allografts. Thus, these data show the potential of dimeric MHC molecules to promote graft survival and allow visualization of alloreactive T cells.

Key Words: transplantation • tolerance • soluble MHC • visualization