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

Buka Samten, James C. Townsend, Zvjezdana Sever-Chroneos, Virginia Pasquinelli, Peter F. Barnes, Zissis Chroneos

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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-SPR210n 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.

Original languageEnglish (US)
Pages (from-to)115-123
Number of pages9
JournalJournal of Leukocyte Biology
Volume84
Issue number1
DOIs
StatePublished - Jul 1 2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this