CD11c(+) eosinophils in the murine thymus: Developmental regulation and recruitment upon MHC class I-restricted thymocyte deletion

Eosinophils are bone marrow-derived cells released into the circulation dur ing hypersensitivity reactions and parasitic infections. Under normal condi tions most eosinophils are tissue bound, where their physiologic role is un clear. During in situ analysis of the thymic microenvironment for CD11c(+) dendritic cell subpopulations (APC critical in the process of thymic negati ve selection) a discrete population of CD11b/CD11c double-positive cells co ncentrated in the cortico-medullary region of young mice was detected. Thym ic CD11c(+) cells were isolated, and the CD11b(+) subpopulation (CD44(high) , class IIlow, CD11c(int)) was identified as mature eosinophils based on: s catter characteristics, major basic protein mRNA expression, and eosinophil ic granules. They are hypodense, release high levels of superoxide anion, a nd express CD25, CD69, and mRNA for IL-4 and IL-13, but not GM-CSF or IL-5, suggesting a distinct state of activation. Thymic eosinophils are preferen tially recruited during the neonatal period; absolute numbers increased 10- fold between 7-14 days to reach parity with dendritic cells before diminish ing. In a model of acute negative selection, eosinophil numbers were increa sed 2-fold 6 h after cognate peptide injection into MHC class I-restricted female H-Y TCR transgenic mice. In both peptide-treated female and negative ly selecting male H-Y TCR mice, clusters of apoptotic bodies were associate d with eosinophils throughout the thymus, Our data demonstrate a temporal a nd spatial association between eosinophil recruitment and class I-restricte d selection in the thymus, suggesting an immunomodulatory role for eosinoph ils under nonpathological conditions.