A novel murine model for the assessment of human CD2-related reagents in vivo.
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.
Ding
Y
Y
Department of Microbiology, University of Michigan, Ann Arbor, MI 48109, USA.
Qin
L
L
Yang
Q
Q
Punch
J D
JD
Fox
D A
DA
Hochman
P S
PS
Bromberg
J S
JS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018801:CD2 Antigens / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D018968:CD58 Antigens / Q000235:genetics / Q000494:pharmacology; D016827:CD8 Antigens / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007202:Indicators and Reagents; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D018968:CD58 Antigens; D016827:CD8 Antigens; D007166:Immunosuppressive Agents; D007202:Indicators and Reagents; D011993:Recombinant Fusion Proteins