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Journal of Assisted Reproduction and Genetics

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01-03-2008 | Assisted Reproduction

CD200-dependent and nonCD200-dependant pathways of NK cell suppression by human IVIG

Authors: David A. Clark, Karrie Wong, Daljeet Banwatt, Ziqhi Chen, Jian Liu, Lydia Lee, Reginald M. Gorczynski, Morris A. Blajchman

Published in: Journal of Assisted Reproduction and Genetics | Issue 2-3/2008

Abstract

Problem

Intravenous immunoglobulin (IVIG) has been used to suppress autoimmune and inflammatory disorders by a variety of mechanisms. Recently, the CD200 tolerance-promoting signal has been found to play a role in IVIG suppression of blood natural killer (NK) cells. Further, different types of IVIG have been reported to differ in this activity, and that has been related to efficacy (and inefficacy) of treatment of women with pregnancy failure. CD200 acts by binding to CD200 receptors (C200R). The objective of this study was to determine if CD200-dependent NK suppression by IVIG involved direct binding of IVIG-associated CD200 molecules to CD200R on NK cells.

Method of study

Peripheral Blood Lymphocytes isolated from human blood were used as a source of NK cells to lyse Cr⁵¹-labelled K562 target cells in vitro in 18 and 4 h assays, and three different types of IVIG were tested for suppressive activity in the presence or absence of specific monoclonal anti-huCD200. In some experiments, CD56⁺ NK cells were purified using anti-CD56 magnetic beads. Western blotting of IVIG using a specific anti-huCD200 antibody was done. Enzyme-Linked ImmunoSorbent Assays were used to measure cytokine production in NK assays.

Results

Different IVIGs showed significant differences in potency in suppressing NK cytolytic activity in vitro (mg/ml for 60% suppression, Gammagard 4.1, Gamunex 14.1, Gamimmune 20.2). For CD200-dependent suppression, Gammagard was twice as potent as Gamimmune, but equivalent to Gamunex. The presence of suppression in 4 hour assays indicated stimulation of cytokine synthesis was unlikely to explain CD200-dependent suppression. Purification of NK cells led to loss of the CD200-dependent component. Western blotting confirmed that material reactive with anti-CD200 antibody was present in Immunoglobulin G (IgG) preparations, and at a lower level in human serum that contains IgG.

Conclusions

IVIGs are not all equipotent in suppressing NK cell cytolytic activity. CD200 associated with IVIG is an important component of suppression. CD200-dependent suppression appears to be mediated by a non-NK population that then acts on NK cells by direct contact rather than indirectly through release of immunosuppressive cytokines.

Darabi K, Abdel Wahab O, Dzik WH. Current usage of intravenous immune globulin and the rationale behind it: the Massachusetts General Hospital data and a review of the literature. Transfusion. 2006;46:741–53.PubMedCrossRef

Clark DA, Coulam CB, Stricker RM. Is intravenous immunoglobulins (IVIG) efficacious in early pregnancy failure ? A critical review and meta-analysis. J Assist Reprod Genet. 2006;23:1–13. [erratum 2006;23:383].PubMedCrossRef

Hutton B, Sharma R, Fergusson DA, Tinmouth AA, Hebert PC, Jamieson J, Walker M. Use of intravenous immunoglobulin for treatment of miscarriage: a systematic review. BJOG. 2007;114:134–42.PubMedCrossRef

Van den Heuvel M, Peralta CG, Hatta K, Han VK, Clark DA. Decline in number of elevated blood CD3⁺ CD56⁺ NKT cells in response to intravenous immunoglobulin treatment correlates with successful pregnancy. Am J Reprod Immunol. 2007;58:447–59.PubMedCrossRef

Ruiz JE, Kwak JY, Baum L, Gilman-Sachs A, Beaman KD, Kim YB, Beer AE. Intravenous immunoglobulin inhibits natural killer cell activity in vivo in women with recurrent spontaneous abortion. Am J Reprod Immunol. 1996;35:370–5.PubMed

Siragam V, Crow AR, Brinc D, Song S, Freedman J, Lazarus AH. Intravenous immunoglobulin ameliorates ITP via activating Fcγ receptors on dendritic cells. Nature Med. 2006;12:688–92.PubMedCrossRef

Clark DA, Chaouat G. Loss of surface CD200 on stored allogeneic leukocytes may impair anti-abortive effect in vivo. Am J Reprod Immunol. 2005;53:13–20. [erratum 2005;54:124].PubMedCrossRef

Wright GJ, Cherwinski H, Foster-Cuevas M, Brooke G, Puklavec MJ, Bigler M, Song Y, Jenmalm M, Gorman D, McClanahan T, Liu M-R, Brown MH, Sedgewick JD, Phillips JH, Barclay AN. Characterization of the CD200 receptor family in mice and humans and their interaction with CD200. J Immunol. 2003;171:3034–46.PubMed

Gorczynski RM, Chen Z, Clark DA, Yu K, Lee L, Nachman J, Wong S, Marsden P. Structureal and functional heterogeneity in the CD200R family of immunoregulatory molecules at the feto-maternal interface. Am J Reprod Immunol. 2004;52:147–63.PubMedCrossRef

10.

Gorczynski RM, Hadidi S, Yu G, Clark DA. The same immunoregulatory molecules contribute to successful pregnancy and transplantation. Am J Reprod Immunol. 2002;47:1–9.CrossRef

11.

Gorczynski RM, Lee L, Boudakov I. Augmented induction of CD4⁺ CD25⁺ Treg using monoclonal antibodies to CD200R. Transplantation. 2005;79:1180–3.PubMedCrossRef

12.

Yamada H. Recurrent miscarriage, genetic/immunologic factor and immunoglobulin therapy. Am J Reprod Immunol. 2007;58:191.

13.

Stassen M, Fondel S, Bopp T, Richter C, Muller C, Kubach J, Becker C, Knop J, Enk AH, Schmitt S, Jonuleit H. Human CD25⁺ regulatory T cells: two subsets defined by integrins α₄β₇ or α₄β₁ confer distinct suppressive properties on CD4⁺ T helper cells. Eur J Immunol. 2004;34:1303–11.PubMedCrossRef

14.

Nakamura K, Kitani A, Strober W. Cell contact-dependent immunosuppression by CD4⁺ CD25⁺ regulatory T cells is mediated by cell surface-bound transforming growth factor β. J Exp Med. 2001;194:629–44.PubMedCrossRef

15.

Shalev I, Liu H, Koscik C, Bartczak A, Javadi M, Wong K, Maknojia A, He W, Liu MF, Diao J, Cattral M, Gommerman J, Clark DA, Phillips MJ, Gorczynski RM, Zhang L, Downey G, Grant D, Cybulsky MI, Levy GA. Targeted deletion of fgl2 leads to impaired regulatory T cell activity and development of autoimmune disease. J Immunol. 2008;180:249–60.PubMed

16.

Crow AR, Song S, Semple JW, Freedman J, Lazarus AH. Role for IL-1 receptor antagonist or other cytokines in the acute therapeutic effect of IVIG? Blood. 2007;109:155–8.PubMedCrossRef

Title: CD200-dependent and nonCD200-dependant pathways of NK cell suppression by human IVIG
Authors: David A. Clark
Karrie Wong
Daljeet Banwatt
Ziqhi Chen
Jian Liu
Lydia Lee
Reginald M. Gorczynski
Morris A. Blajchman
Publication date: 01-03-2008
Publisher: Springer US
Published in: Journal of Assisted Reproduction and Genetics / Issue 2-3/2008
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-008-9202-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

CD200-dependent and nonCD200-dependant pathways of NK cell suppression by human IVIG

Abstract

Problem

Method of study

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Problem

Method of study

Results

Conclusions

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