Immunocamouflage: prevention of transfusion-induced graft-versus-host disease via polymer grafting of donor cells.
Graft-versus-host disease (GVHD) can occur following the transfer of allogeneic lymphocytes into immunosuppressed and, in rare cases, immunocompetent recipients. The initiation of GVHD requires the allorecognition of the recipient's disparate MHC molecules by the donor T lymphocytes (T cell). Currently, GVHD is controlled by cyclosporine administration--a potent, but toxic, T-cell suppressing agent. To determine if the nontoxic grafting of methoxypoly(ethylene glycol) (mPEG) to immunologically foreign lymphocytes could prevent allorecognition and GVHD, in vitro and in vivo murine studies were performed. In vitro studies utilizing mixed lymphocyte reactions (MLRs) demonstrate that mPEG modification effectively prevented allorecognition and subsequent T-cell proliferation. The loss of cellular proliferation was not due to mPEG cytotoxicity but rather to the inhibition of cell-cell interactions. Flow cytometric studies showed that T-cell and antigen-presenting cell adhesion molecules (CD2, CD11a), signaling (CD3epsilon, T-cell receptor), and costimulatory molecules (CD28, CD80) were efficiently immunocamouflaged by mPEG derivatization. Interestingly, upon antigenic stimulation mPEG-modified cells demonstrate enhanced apoptosis as evidenced by DNA laddering. In vivo studies using immunocompetent and immunosuppressed mice established that mPEG modification of donor lymphocytes effectively attenuated the in vivo proliferation of donor cells and the initiation of GVHD.
Chen
Audrey M
AM
Department of Neurology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA.
Scott
Mark D
MD
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001803:Blood Transfusion; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D011092:Polyethylene Glycols / Q000494:pharmacology; D013154:Spleen / Q000637:transplantation; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol