Impaired maintenance of naturally acquired T-cell memory to the meningococcus in patients with B-cell immunodeficiency

Garcez, Tomaz Pereira; Morales-Aza, Begonia; Glennie, Sarah J.; Davenport, Victoria; Johnston, Sarah L.; Williams, Neil A.; Heyderman, Robert S.

Abstract

The importance of T cells in the generation of antigen-specific B-cell immunity has been extensively described, but the role B cells play in shaping T-cell memory is uncertain. In healthy controls, exposure to Neisseria meningitidis in the upper respiratory tract is associated with the generation of memory T cells in the mucosal and systemic compartments. However, we demonstrate that in B cell-deficient subjects with X-linked agamma-globulinemia (XLA), naturally acquired T-cell memory responses to meningococcal antigens are reduced compared with healthy control patients. This difference is not found in T-cell memory to an obligate respiratory pathogen, influenza virus. Accordingly, we show that meningococcal antigens up-regulate major histocompatibility complex (MHC) class II, CD40, CD86/80 expression on mucosal and systemic associated B cells and that antigen presentation stimulates T-cell proliferation. A similar reduction in N meningitidis but not influenza antigen-specific T-cell memory was observed in subjects with X-linked hyper IgM syndrome (X-HIM), implicating the interaction of CD40-CD40L in this process. Together, these data implicate B cells in the induction and maintenance of T-cell memory to mucosal colonizing bacteria such as N meningitidis and highlight the importance of B cells beyond antibody production but as a target for immune reconstitution. © 2009 by The American Society of Hematology.

• Journal Article Type: Article
• Publication Date: Nov 18, 2009
• Journal: Blood
• Print ISSN: 0006-4971
• Electronic ISSN: 1528-0020
• Publisher: American Society of Hematology
• Peer Reviewed: Peer Reviewed
• Volume: 113
• Issue: 18
• Pages: 4206-4212
• DOI: https://doi.org/10.1182/blood-2008-08-171587
• Keywords: T-cell memory, meningococcus, B-cell immunodeficiency
• Public URL: https://uwe-repository.worktribe.com/output/1004600
• Publisher URL: http://dx.doi.org/10.1182/blood-2008-08-171587