In:
Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2542-2542
Abstract:
Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder that can cause fatal arterial or venous thrombosis/thromboembolism. Immune complexes consisting of heparin, platelet factor 4 (PF4) and PF4/heparin-reactive antibodies are central to the pathogenesis of HIT. Regulatory T (Treg) cells are a subpopulation of CD4 T cells that modulate immune system by suppressing or down-regulating immune response and play an important role in immune homeostasis. However, the role of Treg cells in controlling PF4/heparin-specific antibody production is not known. Here we found that FoxP3-deficient mice, which have no functional Treg cells, spontaneously generated PF4/heparin-specific antibodies as early as three weeks after birth. Similarly, following transplantation with bone marrow cells from FoxP3-deficient mice, Rag1-deficient mice that have no endogenous B cells and T cells spontaneously produced PF4/heparin-specific antibodies. In contrast, Rag1-deficient mice that received wild-type bone marrow cells failed to produce PF4/heparin-specific antibodies. In addition, adoptively transferred Treg cells prevented spontaneous production of PF4/heparin-specific antibodies in FoxP3-deficient mice. Adoptively transferred Treg cells, not conventional CD4 T cells, also suppressed PF4/heparin complex-induced production of PF4/heparin-specific IgGs in wild-type mice. Treg cells suppress immune response mainly through releasing anti-inflammatory cytokines, such as interleukin-10 (IL-10). Deficiency of IL-10 led to spontaneous production of PF4/heparin-specific antibodies in mice. Moreover, BM chimeric mice with CD4 T cell-specific deletion of IL-10 increased PF4/heparin-specific IgG production following PF4/heparin complex challenge. Taken together, these findings demonstrate that Treg cells play an important role in suppressing PF4/heparin-specific antibody production in mice. Disclosures Haribhai: AbbVie Inc.: Employment. Aster:BloodCenter of Wisconsin: Patents & Royalties.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood-2018-99-113049
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2018
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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