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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1207835

Received for publication December 14, 2007.
Revised February 29, 2008.
Accepted for publication March 27, 2008.

Article

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 {dagger}, Virginia Pasquinelli {ddagger}, Peter F. Barnes *, and Zissis C. Chroneos {dagger}

*Department of Microbiology and Immunology and the Center for Pulmonary and Infectious Disease Control and {dagger}Department of Biochemistry, the University of Texas Health Center, Tyler, Texas, USA; and {ddagger}Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina

@ To whom correspondence should be addressed. E-mail: buka.samten{at}uthct.edu.


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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 ({alpha}-SP-R210n) or nonbinding C-terminal domain ({alpha}-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 ({alpha}-SP-R210n) cross-linking the SP-R210 through the SP-A-binding domain markedly inhibited cell proliferation and IFN-{gamma} secretion by PBMC from PPD+ donors in response to heat-killed M. tuberculosis, whereas preimmune IgG and antibodies ({alpha}-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-{alpha} but increased production of IL-10. Inhibition of IFN-{gamma} production by {alpha}-SP-R210n was abrogated by the combination of neutralizing antibodies to IL-10 and TGF-{beta}1. 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-{beta}1.

Key Words: cytokine • tuberculosis




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