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A more recent version of this article appeared on September 1, 2005

Published online before print July 6, 2005
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0205078

Received for publication February 7, 2005.
Revised May 11, 2005.
Accepted for publication May 12, 2005.

Article

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}@

*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

@ To whom correspondence should be addressed. E-mail: nicholas-zavazava{at}uiowa.edu.


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Abstract

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 • concanavalin A • FLAG