Acquisition of Pneumococci Specific Effector and Regulatory Cd4+ T Cells Localising within Human Upper Respiratory-Tract Mucosal Lymphoid Tissue

PLoS Pathogens

William W. Kwok¹  Timothy J. Mitchell²  Jeffrey Pido-Lopez³  Neil A. Williams³  Robert S. Heyderman⁴ 

[1]Benaroya Research Institute at Virginia Mason, Seattle, Washington, United States of America

[2]Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom

[3]School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom

[4]Wellcome Trust Clinical Research Programme, Blantyre, Malawi

关键词: Regulatory T cells;    T helper cells;    T cells;    Tonsils;    Pneumococcus;    Cytokines;    Immune response;    Cell staining;   

DOI  :  10.1371/journal.ppat.1002396

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4+ T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4+ T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25hi T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4+ T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines.

【 授权许可】

CC BY