Impaired maintenance of naturally acquired T-cell memory to the meningococcus in patients with B-cell immunodeficiency
Morales-Aza, B., Glennie, S. J., Garcez, T. P., Davenport, V., Johnston, S. L., Williams, N. A. and Heyderman, R. S. (2009) Impaired maintenance of naturally acquired T-cell memory to the meningococcus in patients with B-cell immunodeficiency. Blood, 113 (18). pp. 4206-4212. ISSN 0006-4971 Available from: http://eprints.uwe.ac.uk/7182
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Publisher's URL: http://dx.doi.org/10.1182/blood-2008-08-171587
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 agammaglobulinemia (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.