Oral tolerance to low dose β2-glycoprotein I: Immunomodulation of experimental antiphospholipid syndrome

Miri Blank, Jacob George, Vivian Barak, Angela Tincani, Takao Koike, Yehuda Shoenfeld

Research output: Contribution to journalArticlepeer-review

Abstract

Oral tolerance was induced in BALB/c mice by feeding low dose β2- glycoprotein I (β2GPI). The β2GPI-fed mice did not develop serologic and clinical markers of experimental antiphospholipid syndrome (APS) upon immunization with the autoantigen. The treated group was characterized by low titers of serum anti-β2GPI and anticardiolipin Abs in the serum, lack of fetal resorptions, low incidence of thrombocytopenia, and normal aPTT (activated partial thromboplastin time) values. β2GPI given orally before priming with β2GPI resulted in complete prevention of experimental APS development; β2GPI given at an early stage of the disease reduced clinical manifestations. However, administration of β2GPI 70 days postimmunization had a less significant effect on disease expression. Tolerized mice exhibited a diminished T lymphocyte proliferation response to β2GPI in comparison with β2GPI-immunized mice fed with OVA. When nontolerant β2GPI-primed T lymphocytes were mixed with T lymphocytes derived from tolerized mice, a significant inhibition of proliferation upon exposure to β2GPI was observed. The induction of suppression was β2GPI specific and driven, as well as TGF-β mediated. The β2GPI-specific response of T lymphocytes from the β2GPI-fed mice was reversed by anti-TGF-β Abs. The tolerance was adoptively transferred by CD8+ T cells from the tolerized mice into naive mice. Those CD8+ cells were MHC class I restricted, found to secrete TGF- β, and had no cytolytic activity. Oral administration of β2GPI suppressed priming of CTLs in the recipient mice. In sum, β2GPI-induced oral tolerance has an immunomodulatory effect in experimental APS, demonstrating the importance of β2GPI in the pathogenesis of the disease.

Original languageEnglish
Pages (from-to)5303-5312
Number of pages10
JournalJournal of Immunology
Volume161
Issue number10
StatePublished - 15 Nov 1998

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