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?? T cells exhibit multifunctional and protective memory in intestinal tissues.

ABSTRACT: The study of T cell memory and the target of vaccine design have focused on memory subsumed by T cells bearing the ?? T cell receptor. Alternatively, ?? T cells are thought to provide rapid immunity, particularly at mucosal borders. Here, we have shown that a distinct subset of mucosal ?? T cells mounts an immune response to oral Listeria monocytogenes (Lm) infection and leads to the development of multifunctional memory T cells capable of simultaneously producing interferon-? and interleukin-17A in the murine intestinal mucosa. Challenge infection with oral Lm, but not oral Salmonella or intravenous Lm, induced rapid expansion of memory ?? T cells, suggesting contextual specificity to the priming pathogen. Importantly, memory ?? T cells were able to provide enhanced protection against infection. These findings illustrate that ?? T cells play a role with hallmarks of adaptive immunity in the intestinal mucosa.

SUBMITTER: Sheridan BS

PROVIDER: S-EPMC3749916 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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γδ T cells exhibit multifunctional and protective memory in intestinal tissues.

Sheridan Brian S BS Romagnoli Pablo A PA Pham Quynh-Mai QM Fu Han-Hsuan HH Alonzo Francis F Schubert Wolf-Dieter WD Freitag Nancy E NE Lefrançois Leo L

Immunity 20130701 1

The study of T cell memory and the target of vaccine design have focused on memory subsumed by T cells bearing the αβ T cell receptor. Alternatively, γδ T cells are thought to provide rapid immunity, particularly at mucosal borders. Here, we have shown that a distinct subset of mucosal γδ T cells mounts an immune response to oral Listeria monocytogenes (Lm) infection and leads to the development of multifunctional memory T cells capable of simultaneously producing interferon-γ and interleukin-17 ...[more]

PMID: 23890071

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Project description:BackgroundCytokine-induced memory-like natural killer (CIML NK) cells have been found to possess potent antitumor responses and induce complete remissions in patients with leukemia. However, the poor infiltration of transferred NK cells is a major obstacle in developing adoptive cell immunotherapy for solid tumors. In our study, we explored the potential of using the tumor-penetrating peptide iRGD to deliver activated CIML NK cells deep into tumor tissues.MethodsAfter being briefly stimulated with interleukin-12 (IL-12), IL-15, and IL-18, CIML NK cells were assessed for their phenotype and function with flow cytometry. The penetrating and killing capability of iRGD-modified CIML NK cells in tumor spheroids was revealed by confocal microscopy. The anti-tumor efficacy of these modified CIML NK cells was tested in hepatocellular carcinoma (HCC) xenograft mouse models.ResultsTreating NK cells with cytokines led to a substantial activation, which was evidenced by the upregulation of CD25 and CD137. After a resting period of six days, CIML NK cells were still able to display strong activation when targeting HepG2 and SK-Hep-1 HCC cell lines. Additionally, CIML NK cells produced increased amounts of cytokines (interferon-gamma and tumor necrosis factor alpha) and exhibited heightened cytotoxicity towards HCC cell lines. The iRGD modification enabled CIML NK cells to infiltrate multicellular spheroids (MCSs) and, consequently, to induce cytotoxicity against the target cancer cells. Moreover, the CIML NK cells modified with iRGD significantly decreased tumor growth in a HCC xenograft mouse model.ConclusionOur findings demonstrate that CIML NK cells possess augmented potency and durability against HCC cell lines in vitro. Additionally, we have seen that the incorporation of iRGD to CIML NK cells facilitates enhanced infiltration and targeted destruction of MCSs. Moreover, the application of iRGD-modified CIML NK cells reveal remarkable anti-tumor efficacy against HCC in vivo.

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?? T cells exhibit multifunctional and protective memory in intestinal tissues.

Publications

γδ T cells exhibit multifunctional and protective memory in intestinal tissues.

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