Antisense deoxyoligonucleotides or antibodies to murine MD-1 inhibit rejection of allogeneic and xenogeneic skin grafts in C3H mice.

Abstract:

BACKGROUND:Altered expression of murine MD-1, a molecule controlling expression of members of the interleukin (IL)-1 receptor family of signaling proteins, regulates antigen-presenting cell-induced alloreactions. We investigated the effect of treatment with antisense deoxyoligonucleotides or antibodies to MD-1 in vivo on allogeneic and xenogeneic skin graft survival and the immune responses in transplanted mice. METHODS:C3H mice received C57BL/6 or Lewis rat skin grafts, followed by i.v. injections of anti-MD-1 antibody or antisense oligonucleotides or control reagents at 48-hr intervals. Survival was monitored. In separate studies, mice were sacrificed at 5-day intervals. Serum was analyzed for circulating MD-1 antigen, and peritoneal cells for surface expression of MD-1. The proliferative and cytolytic response of lymphocytes harvested from treated animals and restimulated in vitro with allo- or xenogeneic cells, and the cytokines produced, was measured. Graft histology was assessed at 11 days after transplantation. RESULTS:Treatment with anti-MD-1 oligonucleotides or antibodies suppressed rejection of both xeno- and allogeneic grafts, decreased induction of graft-specific cytotoxic T cells, increased production of type-2 cytokines (IL-4 and IL-10), and decreased production of type-1 cytokines (IL-2 and interferon-gamma). Serum levels of MD-1 were suppressed, as was expression of MD-1 on the surface of antigen-presenting cells. Grafts from MD-1-treated mice showed little lymphocyte infiltration, and no signs of graft necrosis. CONCLUSION:Our data suggest a critical in vivo role for MD-1 expression in regulating graft rejection, as well as in the concomitant sensitization of T cells and their cytokine production profile, which parallels the rejection response.

journal_name

Transplantation

journal_title

Transplantation

authors

Hadidi S,Chen Z,Phillips J,Yu K,Gorczynski RM

doi

10.1097/00007890-200206150-00013

subject

Has Abstract

pub_date

2002-06-15 00:00:00

pages

1771-9

issue

11

eissn

0041-1337

issn

1534-6080

journal_volume

73

pub_type

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