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

TitleA novel murine model for the assessment of human CD2-related reagents in vivo.
Publication TypeJournal Article
Year of Publication1996
AuthorsDing Y, Qin L, Yang Q, Punch JD, Fox DA, Hochman PS, Bromberg JS
JournalJ Immunol
Date Published1996 Sep 01
KeywordsAnimals, Antibodies, Monoclonal, CD2 Antigens, CD3 Complex, CD4 Antigens, CD58 Antigens, CD8 Antigens, Dermatitis, Contact, Female, Graft Survival, Heart Transplantation, Humans, Immunosuppressive Agents, Indicators and Reagents, Lymphocyte Depletion, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Models, Immunological, Recombinant Fusion Proteins, T-Lymphocytes

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.

Alternate JournalJ Immunol
PubMed ID8757303
Grant ListAI-32655 / AI / NIAID NIH HHS / United States
P60-AR20557 / AR / NIAMS NIH HHS / United States
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Lihui Qin, M.D., Ph.D.

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