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Characterization of a B220⁺ Lymphoid Cell Subpopulation with Immune Modulatory Functions in Nasal-Associated Lymphoid Tissues

Faiza Rharbaoui^*, Dunja Bruder, Melita Vidakovic, Thomas Ebensen^*, Jan Buer^, and Carlos A. Guzmán^1,*

Divisions of ^* Microbiology, Cell Biology and Immunology, and Gene Regulation and Differentiation, GBF-German Research Center for Biotechnology, Braunschweig, Germany; and Institute of Medical Microbiology, Medizinische Hochschule Hannover, Germany

Complex mechanisms operate on mucosal tissues to regulate immune responsiveness and tolerance. When the lymphocyte subpopulations from murine nasal-associated lymphoid tissues (NALT) were characterized, we observed an accumulation of B220^lowCD3^lowCD4^–CD8^–CD19^–c-Kit⁺ cells. TCR transgenic mice and athymic mice were used for monitoring T cell lineage and the presence of extrathymic T cell precursors. The majority of cells from NALT exhibited a T cell precursor phenotype (CD4^–CD8^–CD19^–c-Kit⁺). Fas-independent apoptosis was their main mechanism of cell death. We also demonstrated that B220^lowCD4^–CD8^–CD19^– cells from NALT exhibited the potential to down-regulate the activation of mature T cells. However, the innate immunity receptor TLR2 was also highly expressed by this cell subpopulation. Moreover, nasal stimulation with a TLR2/6 agonist resulted in a partial activation of the double-negative cells. These results suggest that the immune responses in NALT may be in part modulated by a cell subpopulation that maintains a tolerogenic milieu by its proapoptotic status and suppressive activity, which can be reverted through stimulation of a TLR signaling cascade.

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