Giri , S and Meitei, HT and Sonar, AS and Shaligram, S and Lal, G (2022) In vitro-induced Foxp3+ CD8+ regulatory T cells suppress allergic IgE response in the gut. Journal of Leukocyte Biology.

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Abstract

Several subsets of CD8+ T cells are known to have a suppressive function in different tissues and diseases in mice and humans. Due to the lack of a consensus on the phenotype of regulatory CD8+ T cells and very low frequency in the body, its clinical use as adoptive cellular therapy has not advanced much. In the present work, using DNA methyltransferase inhibitor 5-Aza-2′-deoxycytidine (Aza), we efficiently and stably differentiated naïve CD8+ T cells (CD8+CD25–CD44– cells) into the CD8+Foxp3+ regulatory CD8+ T cells (CD8 Tregs). We also generated OVA peptide257-264-specific CD8+Foxp3+ Tregs. Compared with activated CD8 T cells, Aza plus TGF-β-induced CD8+Foxp3+ Tregs showed significantly increased surface expression of CD39, CD73, CD122, CD62L, and CD103, and secreted TGF-β and suppressed the proliferation of effector CD4+ T cells. Interestingly, CD8+Foxp3+ Tregs exhibited low expression of perforin and granzyme required for cytotoxic function. Analysis of chemokine receptors showed that TGF-β + Aza induced CD8+Foxp3+ Tregs expressed gut-tropic chemokine receptors CCR6 and CCR9, and chemokine receptors CCR7 and CXCR3 required for mobilization into the spleen, lymph nodes, and gut-associated lymphoid tissues. Adoptive transfer of induced CD8+Foxp3+ Tregs restored cholera toxin-induced breakdown of oral tolerance to OVA by regulating OVA-specific IgE and IgG1. Altogether, we showed an efficient method to generate antigen-specific CD8+Foxp3+ Tregs, and the adoptive transfer of these cells induces oral tolerance by suppressing allergic response and maintaining intestinal homeostasis.

Item Type:	Article
Subjects:	Infection and Immunity
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	20 Oct 2022 10:36
Last Modified:	20 Oct 2022 10:36
URI:	http://nccs.sciencecentral.in/id/eprint/1200

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