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An antibody against the surfactant protein A (SP‐A)‐binding domain of the SP‐A receptor inhibits T cell‐mediated immune responses to Mycobacterium tuberculosis
Author(s) -
Samten Buka,
Townsend James C.,
SeverChroneos Zvjezdana,
Pasquinelli Virginia,
Barnes Peter F.,
Chroneos Zissis C.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1207835
Subject(s) - biology , antibody , immune system , mycobacterium tuberculosis , microbiology and biotechnology , peripheral blood mononuclear cell , secretion , t cell , immunology , tuberculosis , biochemistry , in vitro , medicine , pathology
Surfactant protein A (SP‐A) suppresses lymphocyte proliferation and IL‐2 secretion, in part, by binding to its receptor, SP‐R210. However, the mechanisms underlying this effect are not well understood. Here, we studied the effect of antibodies against the SP‐A‐binding (neck) domain (α‐SP‐R210n) or nonbinding C‐terminal domain (α‐SP‐R210ct) of SP‐R210 on human peripheral blood T cell immune responses against Mycobacterium tuberculosis . We demonstrated that both antibodies bind to more than 90% of monocytes and 5–10% of CD3+ T cells in freshly isolated PBMC. Stimulation of PBMC from healthy tuberculin reactors [purified protein derivative‐positive (PPD+)] with heat‐killed M. tuberculosis induced increased antibody binding to CD3+ cells. Increased antibody binding suggested enhanced expression of SP‐R210, and this was confirmed by Western blotting. The antibodies (α‐SP‐R210n) cross‐linking the SP‐R210 through the SP‐A‐binding domain markedly inhibited cell proliferation and IFN‐γ secretion by PBMC from PPD+ donors in response to heat‐killed M. tuberculosis , whereas preimmune IgG and antibodies (α‐SP‐R210ct) cross‐linking SP‐R210 through the non‐SP‐A‐binding, C‐terminal domain had no effect. Anti‐SP‐R210n also decreased M. tuberculosis ‐induced production of TNF‐α but increased production of IL‐10. Inhibition of IFN‐γ production by α‐SP‐R210n was abrogated by the combination of neutralizing antibodies to IL‐10 and TGF‐β1. Together, these findings support the hypothesis that SP‐A, via SP‐R210, suppresses cell‐mediated immunity against M. tuberculosis via a mechanism that up‐regulates secretion of IL‐10 and TGF‐β1.