Comparative Studies of Specific Acquired Systemic Tolerance Induced by Intrathymic Inoculation of a Single Synthetic Wistar-Furth (Rt1u) Allo-MHC Class I (RT1.AU) Peptide or Wag (Rt1u)-Derived Class I Peptide1

Abstract

Of interest is our finding that IT injection of a short segment of WAG-derived MHC class I peptide induces active acquired tolerance similar to results obtained with the use of pure WF-derived peptide u-5 in the WF-to-ACI rat combination. It is noteworthy that we could not confirm the T helper (Th)1/Th2 paradigm in this model by initial cytokine analysis. Whether induction of tolerance by IT injection of allo-MHC peptides will have clinical usefulness must await results of similar studies in large animals. However, of major interest is the finding that a short segment of RT1.AU represents the tolerogenic

Biological and Biomaterial Approaches for Improved Islet Transplantation

“…Use of N-monomethyl arginine (Xenos et al, 1994) Ex vivo gene knockdown of inducible nitric-oxide synthase T-cell activation Anti-CD4 Ig to prevent T-cell activation (Shizuru et al, 1987;Lehmann et al, 1997) Anti-CD154 (anti-CD40L) Ig to cause T-cell anergy Zheng et al, 1999) Intrathymic administration of MHC peptides (Chowdhury et al, 1998) Coimplantation of soluble Fas ligand to cause apoptosis of T-cells (Judge et al, 1998) Anti-CD45 antibody (Basadonna et al, 1998) Use of CTLA4-Ig fusion protein (Tran et al, 1997) APPROACHES FOR IMPROVING ISLET TRANSPLANTATION I antigens. Coating with an antibody that does not elicit a host immune response has been used to protect islet grafts against immune destruction.…”

“…T-cells undergo maturation in the thymus gland before being released in blood, and thymus is where self-versus nonself-antigen recognition is implemented by both positive and negative selection. An attractive approach that stems from this mechanism is to inject alloantigens directly into the thymus before graft transplantation to develop selective graft tolerance (Chowdhury et al, 1998). Intrathymic injection of a limited number of islets, or spleen tissue for presenting alloantigens, induces host T-cell tolerance to the subsequent extrathymic islet allotransplantation.…”

CD25+ Immunoregulatory CD4 T Cells Mediate Acquired Central Transplantation Tolerance

“…We and others have previously proposed that clonal deletion of Ag-reactive T cells may be predominantly responsible (6 -10). However, this mechanism cannot account for the observation that depletion of already mature peripheral T cells is not invariably required by these protocols (11)(12)(13)(14). That the introduction of Ag into the thymus may exert a tolerogenic effect on an already established peripheral immune system requires further explanation.…”

Allopeptide‐pulsed dendritic cells and composite tissue allograft survival

“…These cells were cultured and prepared based on our well-established protocol in the mouse DC with some modification. 7 Briefly, the BM cells were cultured (1-1.5 3 10 6 cells/ml) in a total of 4 ml/well in 6-well plates in the presence of recombinant rat GM-CSF (GM) (1 ng/ml) and IL-4 (1 ng/ml) (R&D Systems, Minneapolis, MN) in RPMI-1640 (Gibco, Grand Island, NY) supplemented with 10% w/v FBS, 2 mM L-glutamine, 0.1 mM nonessential amino acids, 1 mM sodium pyruvate, 100 U/ml penicillin, 100 mg/ml streptomycin, and 5 3 10 À5 M 2-ME (Gibco Lab). Cells were fed on day 3 by replacing half of the medium with fresh medium-containing cytokines.…”

“…The WF (RT1-A u ) immunodominant peptide 5 (residues 93-109) was synthesized by the Peptide Facility of the University of Pittsburgh using the RT1-A u sequences that are previously described by Chowdhury et al 7 Rabbit anti-rat lymphocyte serum (ALS) was obtained from Sera Lab, Accurate Chemical (Westbury, NY).…”