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In vitro TNF blockade enhances ex vivo expansion of regulatory T cells in patients with immune thrombocytopenia
Author(s) -
Zhong Hui,
Bussel James,
Yazdanbakhsh Karina
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13126
Subject(s) - immunology , tumor necrosis factor alpha , blockade , immune system , monocyte , cytokine , antibody , medicine , in vitro , immune thrombocytopenia , autoimmunity , t cell , receptor , biology , biochemistry
Summary Tumour necrosis factor‐α ( TNF ) is an inflammatory cytokine that is elevated in a number of autoimmune diseases including immune thrombocytopenia ( ITP ), a bleeding disorder characterized by low platelet counts. In vitro TNF blockade increases expansion of the regulatory T cell (Treg) IKZF 2 (also termed Helios) subset in T cell‐monocyte cocultures from healthy donors, but its role on proliferative responses of Tregs in ITP patients, who have altered immunoregulatory compartment, remains unclear. TNF in CD 4+ T cells from patients with chronic ITP were elevated and negatively correlated with peripheral Treg frequencies, suggesting a possible inhibitory effect of TNF on ITP Tregs. In vitro antibody neutralization with anti‐ TNF in T cell‐monocyte cocultures resulted in a robust expansion of pre‐existing ITP Tregs, higher than in healthy controls. Similar to the effects of anti‐ TNF antibodies, TNF blockade with antibodies against TNFRSF 1B (anti‐ TNFRSF 1B, previously termed anti‐ TNFRII ) almost doubled ITP Treg expansion whereas neutralization with anti‐ TNFRSF 1A (anti‐ TNFRI ) antibodies had no effect on proliferative responses of Tregs. In addition, TNFRSF 1B levels on ITP Tregs were significantly elevated, which may explain the increased susceptibility of patient Tregs to the actions of TNF blockade. Altogether, these data raise the possibility that TNF blockers, through their ability to increase Treg proliferation, may be efficacious in ITP patients.