The same immunoregulatory molecules contribute to successful pregnancy and transplantation. American journal of reproductive immunology (New York, N.Y. : 1989) [Am J Reprod Immunol] Journal article | | Title | The same immunoregulatory molecules contribute to successful pregnancy and transplantation. | | Author(s) | Gorczynski RM, Hadidi S, Yu G, Clark DA | | Institution | Transplant Research Division, The Toronto Hospital, Ontario, Canada. rgorczynski@uhnres.utoronto.ca | | Source | Am J Reprod Immunol 2002 Jul; 48(1):18-26. | | MeSH | Animals
Antigens, CD
Antigens, Surface
Female
Graft Rejection
Graft Survival
Humans
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Inbred DBA
Organ Transplantation
Pregnancy
Pregnancy, Animal
Research Support, Non-U.S. Gov't
Spleen
Transplantation Tolerance
Transplantation, Homologous
Trophoblasts
| | Abstract | PROBLEM: At least two dendritic cell-associated molecules have been shown to contribute to the successful outcome of organ and tissue allografts in mice, namely CD200 and MD-1. CD200 is up-regulated in rodent transplantation models where successful inhibition of rejection is accomplished, and is believed to signal immunosuppression following engagement of a receptor, CD200R, on macrophages and/or gammadelta T-cell receptor (gammadelta TCR+ cells MD-1 is implicated in controlling expression of costimulatory molecules including CD80/CD86 which induce an immunorejection response, and thus inhibition of MD-1 expression also facilitates increased graft survival MD-1 also stabilizes expression of CD14, part of the receptor complex for LPS. As well as the inhibition of rejection which follows blockade of MD-1 expression and/or augmentation of CD200 expression, an altered polarization in cytokine production is seen, with increased expression of interleukin-4 (IL-4), IL-10 and transforming growth factor-beta (TGF-beta), and decreased IL-2, interferon-gamma (IFN-gamma) and tumor nerosis factor-alpha (TNF-alpha). Successful pregnancy in allopregnant mice also depends upon control of graft rejection mechanisms. Proinflammatory T-helper 1 (Th1) cytokines (TNF-alpha + IFN-gamma + IL-1) have been shown to cause spontaneous abortion in mice by activating a novel prothrombinase, fibrinogen-like peptide (fibroleukin) fgl2, which may promote fibrin deposition in the graft rejection process; expression of IL-10, TGF-beta, and progesterone-induced blocking factor (PIBF) in contrast leads to lowering of abortion rates. Interestingly, the spontaneous abortion rates in abortion-prone CBA x DBA/2 matings and in the low abortion rate CBA x BALB/c matings were lower than the frequency of implantation sites showing fibrin(hi) + fgl2 (mRNA)hi, implying regulation of the pro-abortion consequences of fgl2 expression.
METHODS: We have investigated, by in situ hybridization, CD200, MD-1 and fgl2 expression in implantation sites in different strains of mice, and studied the effects of anti-MD-1, anti-CD200 and CD200Fc immunoadhesin on fetal and allograft survival. The role of indoleamine dioxygenase (IDO) was evaluated.
RESULTS: CD200 mRNA expression occurred in the same sites as fgl2 mRNA. Anti-CD200 antibody raised the abortion rate to predicted levels, and infusion of a CD200 immunoadhesin reduced the abortion rate, as did an anti-MD-1 antibody. The latter also improved organ and tissue graft survival. Suppression by antigen-presenting macrophages triggered by CD200 is dependent upon intact IDO activity.
CONCLUSION: Regulation of CD200 and MD-1 expression may control both pregnancy and allograft survival. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 12322892 |
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