Lung effector memory and activated CD4+ T cells display enhanced proliferation in surfactant protein A-deficient mice during allergen-mediated inflammation.

Abstract

Although many studies have shown that pulmonary surfactant protein (SP)-A functions in innate immunity, fewer studies have addressed its role in adaptive immunity and allergic hypersensitivity. We hypothesized that SP-A modulates the phenotype and prevalence of dendritic cells (DCs) and CD4(+) T cells to inhibit Th2-associated inflammatory indices associated with allergen-induced inflammation. In an OVA model of allergic hypersensitivity, SP-A(-/-) mice had greater eosinophilia, Th2-associated cytokine levels, and IgE levels compared with wild-type counterparts. Although both OVA-exposed groups had similar proportions of CD86(+) DCs and Foxp3(+) T regulatory cells, the SP-A(-/-) mice had elevated proportions of CD4(+) activated and effector memory T cells in their lungs compared with wild-type mice. Ex vivo recall stimulation of CD4(+) T cell pools demonstrated that cells from the SP-A(-/-) OVA mice had the greatest proliferative and IL-4-producing capacity, and this capability was attenuated with exogenous SP-A treatment. Additionally, tracking proliferation in vivo demonstrated that CD4(+) activated and effector memory T cells expanded to the greatest extent in the lungs of SP-A(-/-) OVA mice. Taken together, our data suggested that SP-A influences the prevalence, types, and functions of CD4(+) T cells in the lungs during allergic inflammation and that SP deficiency modifies the severity of inflammation in allergic hypersensitivity conditions like asthma.

• Authors: Amy M Pastva, Sambuddho Mukherjee, Charles Giamberardino, Bethany Hsia, Bernice Lo, Gregory D Sempowski, Jo Rae Wright
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 186 Issue 5 Pg. 2842-9 (Mar 01 2011) ISSN: 1550-6606 [Electronic] United States
• PMID: 21257967 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Allergens
• Pulmonary Surfactant-Associated Protein A
• Ovalbumin

Topics

• Allergens (administration & dosage)
• Animals
• CD4-Positive T-Lymphocytes (immunology, metabolism, pathology)
• Cell Proliferation
• Dendritic Cells (immunology, metabolism, pathology)
• Immunologic Memory (genetics)
• Immunophenotyping
• Inflammation (genetics, immunology, pathology)
• Lung (immunology, metabolism, pathology)
• Lymphocyte Activation (genetics, immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Ovalbumin (administration & dosage)
• Pulmonary Surfactant-Associated Protein A (deficiency, genetics, physiology)
• Respiratory Hypersensitivity (immunology, pathology, prevention & control)
• Severity of Illness Index
• Th2 Cells (immunology, metabolism, pathology)