Cd4 T Cell-mediated Protection from Lethal Influenza: Perforin and Antibody-mediated Mechanisms Give a One-two Punch.
From: Trudeau Institute, Saranac Lake, NY 12983, USA. dbrown@trudeauinstitute
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Sep 2006
- ISSN: 0022-1767
- Volume: 177
- Issue: 5
- Pages: 2888-98
- Medium: Print
- Language: English
- Citation (JAMA): Brown Deborah M, Dilzer Allison M, Meents Dana L, et al. Cd4 T Cell-mediated Protection from Lethal Influenza: Perforin and Antibody-mediated Mechanisms Give a One-two Punch.. J. Immunol. Sep 2006;177:2888-98
Abstract
The mechanisms whereby CD4 T cells contribute to the protective response against lethal influenza infection remain poorly characterized. To define the role of CD4 cells in protection against a highly pathogenic strain of influenza, virus-specific TCR transgenic CD4 effectors were generated in vitro and transferred into mice given lethal influenza infection. Primed CD4 effectors conferred protection against lethal infection over a broad range of viral dose. The protection mediated by CD4 effectors did not require IFN-gamma or host T cells, but did result in increased anti-influenza Ab titers compared with untreated controls. Further studies indicated that CD4-mediated protection at high doses of influenza required B cells, and that passive transfer of anti-influenza immune serum was therapeutic in B cell-deficient mice, but only when CD4 effectors were present. Primed CD4 cells also acquired perforin (Pfn)-mediated cytolytic activity during effector generation, suggesting a second mechanism used by CD4 cells to confer protection. Pfn-deficient CD4 effectors were less able to promote survival in intact BALB/c mice and were unable to provide protection in B cell-deficient mice, indicating that Ab-independent protection by CD4 effectors requires Pfn. Therefore, CD4 effectors mediate protection to lethal influenza through at least two mechanisms: Pfn-mediated cytotoxicity early in the response promoted survival independently of Ab production, whereas CD4-driven B cell responses resulted in high titer Abs that neutralized remaining virus.
Mesh Headings (Keywords): Animals, Antibodies, Viral, CD4-Positive T-Lymphocytes, Cells, Cultured, Hemagglutinins, Viral, Lung, Membrane Glycoproteins, Mice, Mice, Transgenic, Orthomyxoviridae, Orthomyxoviridae Infections, Perforin, Pore Forming Cytotoxic Proteins, Survival Rate, Titrimetry
Check for Full Text / PubMed Unique Identifier (PMID): 16920924
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