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Absence of the “Don’t Eat Me” signal results in aberrant T cell responses to Leishmania major 2260958
Abstract   Peer reviewed

Absence of the “Don’t Eat Me” signal results in aberrant T cell responses to Leishmania major 2260958

Hanna Paton, Prajwal Gurung, Austin Paden and Saurabh` Saini
The Journal of immunology (1950), Vol.215(Supplement_1), vkag1411008
08/01/2026
DOI: 10.1093/jimmun/vkag141.1008

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Abstract

Introduction CD47 is a ubiquitously expressed cell surface protein that regulates immune homeostasis by engaging signal regulatory protein alpha (SIRPa) on phagocytes to inhibit their activation. While the CD47-SIRPa axis is known to regulate both innate immunity and T cell responses in cancer & sterile inflammation, its role in infectious disease is poorly defined. Leishmania major (L. major) is an intracellular protozoan parasite that infects phagocytes. Macrophages and CD4+ T cells are both critical for immunity to L. major infection, so we interrogated the role that “don’t eat me” signals play in immunity to L. major. Methods We infected Cd47-/- & Sirpa-/- mice on a C57BL/6 background subcutaneously in each footpad and harvested draining lymph nodes & spleens at several critical time points for flow cytometry. T cell responses were assessed further by ICS & transcription factor staining. Results Cd47-/- & Sirpa-/- disease is severe. They present increased lesions, swelling, & parasite burden compared to controls. Decrease in T cells & increase in antigen experienced T cells is seen. IFNg & TNFa producers are reduced, likely liable for the severity. Conversely, T cell activation is increased in KO mice during acute disease (15dpi) when severity is similar. Conclusion Further studies are in progress to characterize why Cd47-/- & Sirpa-/- mice fail to control L. major infection despite strong early Th1 responses. This is a novel finding showing CD47-SIRPa is required for protective T cell responses to infection.
Cells - T Cells Cells-Th1/Th2 Cells Infections - Parasitic-Helminth Processes - Phagocytosis Tissues - Skin

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