Human CD36 hi monocytes induce Foxp3 + CD25 + T cells with regulatory functions from CD4 and CD8 subsets
Autor: | Jessica G Lee, Michael Nishimura, Anya Nikolai, Alexander Nelson, Yi Wei Lim, Aleksandra Vuchkovska, Paula White, Kathleen E Jaeger, Makio Iwashima, Katherine L. Knight, Yoichi Seki, Dan Kim, Christina Cunha |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
CD14 T cell Immunology Antigen presentation FOXP3 chemical and pharmacologic phenomena hemic and immune systems Biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Immune system medicine.anatomical_structure Antigen medicine Immunology and Allergy IL-2 receptor CD8 030215 immunology |
Zdroj: | Immunology. 163:293-309 |
ISSN: | 1365-2567 0019-2805 |
Popis: | The fetal and neonatal immune systems are uniquely poised to generate tolerance to self, maternal, and environmental antigens encountered in the womb and shortly after birth. However, the tolerogenic nature of fetal and neonatal immunity can be detrimental in the context of pathogens, leading to overwhelming bacterial infections or chronic viral infections. A variety of mechanisms contribute to fetal and neonatal tolerance, including a propensity to generate Foxp3+ regulatory T cells (Treg cells). However, the mechanism(s) of fetal Foxp3+ T cell differentiation, the specific antigen-presenting cells required, and factors that inhibit Treg generation after the neonatal period are poorly understood. Here, we demonstrate that a subset of CD14+ monocytes expressing the scavenger molecule, CD36, can generate CD4+ and CD8+ T cells that co-express Foxp3 and T-bet from both umbilical cord blood. These Foxp3+ T-bet+ T cells potently suppress T cell proliferation and ameliorate xenogeneic graft versus host disease. CD14+ CD36+ monocytes provide known Treg-inducing signals: membrane-bound transforming growth factor-beta and retinoic acid. Unexpectedly, adult peripheral blood monocytes are also capable of inducing Foxp3+ T cells from both cord blood and adult peripheral naive T cells. The induction of Foxp3+ T cells in umbilical cord blood by monocytes was inhibited by the lymphoid fraction of adult peripheral blood cells. These studies highlight a novel immunoregulatory role of monocytes and suggest that antigen presentation by CD36hi monocytes may contribute to the peripheral development of Foxp3+ T-bet+ T cells with regulatory functions in both neonates and adults. |
Databáze: | OpenAIRE |
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