T cell derived IL-10 is dispensable for tolerance induction in a murine model of allergic airway inflammation

Regulatory mechanisms initiated by allergen-specific immunotherapy are mainly attributed to T cell derived IL-10. However, it has not been shown that T cell derived IL-10 is required for successful tolerance induction (TI). Here, we analyze cellular sources and the functional relevance of cell type specific IL-10 during TI in a murine model of allergic airway inflammation. While TI was effective in IL-10 competent mice, neutralizing IL-10 prior to tolerogenic treatment completely abrogated the beneficial effects. Cellular sources of IL-10 during TI were identified by using transcriptional reporter mice as T cells, B cells, and to a lesser extent DCs. Interestingly, TI was still effective in mice with T cell, B cell, B and T cell, or DC-specific IL-10 deficiency. In contrast, TI was not possible inmice lacking IL-10 in all hematopoetic cells, while it was effective in bone marrow (BM) chimera that lacked IL-10 only in nonhematopoetic cells. Taken together, allergen-specific tolerance depends on IL-10 from hematopoetic sources. The beneficial effects of allergen-specific immunotherapy cannot solely be attributed to IL-10 from T cells, B cells, or even DCs, suggesting a high degree of cellular redundancy in IL-10-mediated tolerance.