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 language | English (US) |
|---|---|
| Pages (from-to) | 115-123 |
| Number of pages | 9 |
| Journal | Journal of Leukocyte Biology |
| Volume | 84 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 1 2008 |
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All Science Journal Classification (ASJC) codes
- Cell Biology
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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. / Samten, Buka; Townsend, James C.; Sever-Chroneos, Zvjezdana; Pasquinelli, Virginia; Barnes, Peter F.; Chroneos, Zissis.
In: Journal of Leukocyte Biology, Vol. 84, No. 1, 01.07.2008, p. 115-123.Research output: Contribution to journal › Article
TY - JOUR
T1 - 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
AU - Samten, Buka
AU - Townsend, James C.
AU - Sever-Chroneos, Zvjezdana
AU - Pasquinelli, Virginia
AU - Barnes, Peter F.
AU - Chroneos, Zissis
PY - 2008/7/1
Y1 - 2008/7/1
N2 - 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.
AB - 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.
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U2 - 10.1189/jlb.1207835
DO - 10.1189/jlb.1207835
M3 - Article
C2 - 18443188
AN - SCOPUS:46949106463
VL - 84
SP - 115
EP - 123
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 1
ER -