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The Journal of Immunology, Vol 157, Issue 5 1863-1869, Copyright © 1996 by American Association of Immunologists

ARTICLES

A novel murine model for the assessment of human CD2-related reagents in vivo

Y Ding, L Qin, Q Yang, JD Punch, DA Fox, PS Hochman and JS Bromberg
Department of Microbiology, University of Michigan, Ann Arbor, MI 48109, USA.

CD2 is a T cell surface glycoprotein that mediates both cell-cell adhesion and transmembrane signal transduction. To construct a model for the in vivo evaluation of human (h)CD2 function and hCD2-related reagents, hCD2 transgenic mice and murine (m)CD2 knockout mice were crossed, and the F2 generation selected for mCD2-hCD2+ animals by fluorescent flow cytometry. The mCD2-hCD2+ mice are healthy and have a normal distribution of mCD3, mCD4, and mCD8 in thymus, spleen, and lymph node. Therefore expression of the hCD2 transgene does not appear to disrupt normal T cell development. The functionality of hCD2 was demonstrated by T lymphocyte proliferation upon stimulation by combined anti-CD2 plus anti-CD2R (anti-T11(2) plus anti-T11(3)) mAbs. Anti- T11(2) plus anti-T11(3) anti-human CD2 mAbs also induced proliferation of mCD2+hCD2+ F1 lymphocytes, but not mCD2+hCD2- wild-type murine lymphocytes. Either an anti-murine or the human CD2 specific (anti- T11(1)) mAbs inhibited proliferation in alloantigen, PHA, or anti-CD3 mAb stimulated cultures and inhibited only cells bearing the appropriate cognate CD2. In vivo studies of immune function yielded results consistent with these in vitro assays. Thus, anti-T11(1) mAb suppressed contact sensitivity in vivo in the transgenic/knockout mice. mCD2-hCD2+ mice treated with anti-T11(1) or LFA-3 fusion proteins also showed significant prolongation of cardiac allograft survival. This prolongation was associated both with depletion and down-modulation of CD2 on remaining T cells. These data suggest that the transgenic/knockout mice provide a useful in vivo model for the assessment of hCD2-related reagents and CD2 function, free from any potential interactions with mCD2 and mCD2 ligands.




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