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Blood, Vol. 94 No. 6 (September 15), 1999:
pp. 2135-2141
Stealth Cells: Prevention of Major Histocompatibility
Complex Class II-Mediated T-Cell Activation by Cell
Surface Modification
Kari L. Murad,
Edmund J. Gosselin,
John W. Eaton, and
Mark D. Scott
From the Division of Experimental Pathology and the Department of
Microbiology and Immunology, Albany Medical College, Albany, NY;
and the Department of Pediatrics, Baylor College of Medicine, Houston,
TX.
Transfusion or transplantation of T lymphocytes into an allogeneic
recipient can evoke potent immune responses including, in
immunocompromised patients, graft-versus-host disease (GVHD). As our
previous studies demonstrated attenuated immunorecognition of red blood
cells covalently modified with methoxy(polyethylene glycol) (mPEG), we
hypothesized that T-cell activation by foreign antigens might similarly
be prevented by mPEG modification. Mixed lymphocyte reactions (MLR)
using peripheral blood mononuclear cells (PBMC) from HLA class II
disparate donors demonstrate that mPEG modification of PBMC effectively
inhibits T-cell proliferation (measured by 3H-thymidine
incorporation) in a dose-dependent manner. Even slight derivatization
(0.4 mmol/L mPEG per 4 × 106 cells) resulted in a  75%
decrease, while higher concentrations caused 96% decrease in
proliferation. Loss of PBMC proliferation was not due to either
mPEG-induced cytotoxicity, as viability was normal, or cellular anergy,
as phytohemagglutinin (PHA)-stimulated mPEG-PBMC demonstrated normal
proliferative responses. Addition of exogenous interleukin (IL)-2 also
had no proliferative effect, suggesting that the mPEG-modified T cells
were not antigen primed. Flow cytometric analysis demonstrates that
mPEG-modification dramatically decreases antibody recognition of
multiple molecules involved in essential cell:cell interactions,
including both T-cell molecules (CD2, CD3, CD4, CD8, CD28, CD11a,
CD62L) and antigen-presenting cell (APC) molecules (CD80, CD58, CD62L)
likely preventing the initial adhesion and costimulatory events
necessary for immune recognition and response.
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