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Cellular and molecular cross talk between basophils and CD4+ T cells

Abstract : Basophils are the rare granulocytes and play an important role in the polarization of Th2 responses, differentiation of B cells and protection against helminths. Basophils have a major influence on immune responses and various roles of these cells in autoimmune and inflammatory diseases are emerging. Recent reports showed that murine basophils function as antigen presenting cells (APCs) to induce Th2 and IgE responses to allergens and helminths. Therefore, I explored whether human basophils possess the features of APCs. I found that unlike dendritic cells (DCs) and monocytes, steady-state circulating human basophils did not express HLA-DR and co-stimulatory molecules CD80 and CD86. Basophils remained negative for these molecules following stimulation with various allergens, toll-like receptor ligands and IgE cross-linking.Unlike DCs, basophils did not promote Th2 and Th17 responses. Together, these results demonstrate the inability of circulating human basophils to function as professional APC. Further, basophils were also reported to be implicated in the pathogenesis of Th2 –associated and B cell-mediated autoimmune and inflammatory diseases. Considering the impact of dysregulated function of basophils on the outcome immune responses in various pathological conditions, it was essential to investigate the regulatory mechanisms by which basophil functions are kept in check. As CD4+CD25+FoxP3+ regulatory T cells (Tregs) are critical for the maintenance of immune homeostasis, I sought to investigate the interaction of Tregs with human basophils and its repercussion on basophil functions. My results indicated that unlike other immune cells that aresusceptible to Treg-mediated suppression, basophils are refractory to regulatory mechanism of Tregs. On the contrary I found that T cells could promote activation of basophils. My results thus provided an insight on cellular and molecular basis of regulation of human basophil functions. These data will have a repercussion in understanding role of basophils ininflammatory conditions and in designing therapeutic strategies.
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Submitted on : Monday, September 22, 2014 - 3:37:10 PM
Last modification on : Monday, April 19, 2021 - 8:52:32 AM
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  • HAL Id : tel-01066885, version 1

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Meenu Sharma. Cellular and molecular cross talk between basophils and CD4+ T cells. Biotechnology. Université de Technologie de Compiègne, 2014. English. ⟨NNT : 2014COMP1771⟩. ⟨tel-01066885⟩

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