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Kimmel Cancer Institute, Jefferson Medical College, Philadelphia, PA 19107
The efficacy of a synthetic peptide analogue (rD-mPGPtide),
mimicking the CDR3 region in the first domain of the CD4 surface
molecule, was investigated in a murine model for CD4+
T cell-mediated skin allograft rejection. A single injection of
rD-mPGPtide shortly before transplantation exhibited significantly
prolonged graft survival in the B6 anti-B6.C-H2bm12 MHC
class II-disparate strain combination. Long-term graft survival (>100
days) was achieved when thymectomized adult recipient mice were
transplanted along with rD-mPGPtide treatment. The peptide also
affected secondary rechallenge responses with MHC class II allografts.
In addition, the inhibitory effect of the rD-mPGPtide in this
transplantation model was directed against CD4+ T cells and
was exclusively specific toward donor alloantigen. In vitro analysis of
CD4+ T cells isolated from the draining lymph nodes of
rD-mPGPtide-treated recipients indicated a 450-fold decrease in
precursor frequency in response to donor allostimulation compared with
the untreated control group. There was also significant down-regulation
of the frequency of IL-2-, IFN-
-, and IL-4-producing
CD4+ T cells upon in vitro allogeneic restimulation of host
cells 4 days posttransplantation. However, these same CD4+
T cells maintained the capacity to produce normal cytokine levels upon
third-party allostimulation. Thus, these studies demonstrate that a
CD4-CDR3 peptide analogue can specifically and effectively prolong skin
graft survival across MHC class II barriers.
This article has been cited by other articles:
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  B. MURPHY and A. M. KRENSKY HLA-Derived Peptides as Novel Immunomodulatory Therapeutics J. Am. Soc. Nephrol., June 1, 1999; 10(6): 1346 - 1355. [Abstract] [Full Text]
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