Surfactant protein A integrates activation signal strength to differentially modulate T cell proliferation

Sambuddho Mukherjee, Charles Giamberardino, Joseph Thomas, Kathy Evans, Hisatsugu Goto, Julie G. Ledford, Bethany Hsia, Amy M. Pastva, Jo Rae Wright

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Pulmonary surfactant lipoproteins lower the surface tension at the alveolar-airway interface of the lung and participate in host defense. Previous studies reported that surfactant protein A (SP-A) inhibits lymphocyte proliferation.We hypothesized that SP-A- mediated modulation of T cell activation depends upon the strength, duration, and type of lymphocyte activating signals. Modulation of T cell signal strength imparted by different activating agents ex vivo and in vivo in different mouse models and in vitro with human T cells shows a strong correlation between strength of signal (SoS) and functional effects of SP-A interactions. T cell proliferation is enhanced in the presence of SP-A at low SoS imparted by exogenous mitogens, specific Abs, APCs, or in homeostatic proliferation. Proliferation is inhibited at higher SoS imparted by different doses of the same T cell mitogens or indirect stimuli such as LPS. Importantly, reconstitution with exogenous SP-A into the lungs of SP-A -/- mice stimulated with a strong signal also resulted in suppression of T cell proliferation while elevating baseline proliferation in unstimulated T cells. These signal strength and SP-A-dependent effects are mediated by changes in intracellular Ca 2+ levels over time, involving extrinsic Ca 2+-activated channels late during activation. These effects are intrinsic to the global T cell population and are manifested in vivo in naive as well as memory phenotype T cells. Thus, SP-A appears to integrate signal thresholds to control T cell proliferation.

Original languageEnglish (US)
Pages (from-to)957-967
Number of pages11
JournalJournal of Immunology
Volume188
Issue number3
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Surfactant protein A integrates activation signal strength to differentially modulate T cell proliferation'. Together they form a unique fingerprint.

Cite this