Open AccessSELECTIVE DELETION OF ANTIGEN-SPECIFIC, ACTIVATED T CELLS BY A HUMANIZED MAB TO CD2 (MEDI-507) IS MEDIATED BY NK CELLS
Author(s) -
Luis M. Branco,
Philip Barren,
Su-Yau Mao,
David S. Pfarr,
R. E. Kaplan,
Christina E. Postema,
Solomon Langermann,
Scott Koenig,
Syd Johnson
Publication year - 1999
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/00007890-199911270-00026
Subject(s) - cytotoxic t cell , microbiology and biotechnology , cell sorting , mixed lymphocyte reaction , interleukin 21 , biology , antigen , t cell , natural killer cell , antigen presenting cell , t lymphocyte , interleukin 12 , immunology , flow cytometry , chemistry , immune system , in vitro , biochemistry
CD2 is a 50-kDa transmembrane glycoprotein that plays an important role in T and natural killer (NT) lymphocyte functions. CD2 serves as both an adhesion molecule and as a costimulatory molecule through interactions with its ligand, CD58, on antigen presenting or target cells. Consistent with earlier studies using a rat anti-CD2 mAb, we have shown that treatment of alloantigen stimulated T lymphocytes with a humanized mAb, MEDI-507 (IgG1, kappa), induced hyporesponsiveness to subsequent stimulation with alloantigen but not to mitogen (phytohemagglutinin). Fluorescence-activated cell sorting analysis of cells from mixed lymphocyte reaction (MLR) treated with MEDI-507 revealed pronounced deletion of T and NK cells, consistent with lack of proliferation in the MLR. MEDI-507 F(ab')2 fragments did not have inhibitory activity or induce deletion of lymphocytes in the MLR. Removal of the NK cell subset by magnetic bead depletion using anti-CD16 and anti-CD56 mAbs eliminated both the T cell deletion and the inhibitory effect. Reconstitution of NK depleted responder populations using autologous NK cells restored the MEDI-507-mediated deletion activity to levels measured in the original MLR. Formaldehyde-fixed NK cells failed to mediate the MEDI-507-induced deletion effect. Altogether, our studies indicate that activated T cells with MEDI-507 bound to CD2 are preferential targets for autologous NK cells through a nonapoptotic cytotoxic mechanism.