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Conventional CD4⁺ T cells present bacterial antigens to induce cytotoxic and memory CD8⁺ T cell responses.

ABSTRACT: Bacterial phagocytosis and antigen cross-presentation to activate CD8⁺ T cells are principal functions of professional antigen presenting cells. However, conventional CD4⁺ T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8⁺ T cells, which proliferate and become cytotoxic in response. CD4⁺ T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8⁺ T cells with low PD-1 expression. Moreover, transphagocytic CD4⁺ T cells induce protective anti-tumour immune responses by priming CD8⁺ T cells, highlighting the potential of CD4⁺ T cells as a tool for cancer immunotherapy.

SUBMITTER: Cruz-Adalia A

PROVIDER: S-EPMC5691066 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses.

Cruz-Adalia Aránzazu A Ramirez-Santiago Guillermo G Osuna-Pérez Jesús J Torres-Torresano Mónica M Zorita Virgina V Martínez-Riaño Ana A Boccasavia Viola V Borroto Aldo A Martínez Del Hoyo Gloria G González-Granado José María JM Alarcón Balbino B Sánchez-Madrid Francisco F Veiga Esteban E

Nature communications 20171117 1

Bacterial phagocytosis and antigen cross-presentation to activate CD8+ T cells are principal functions of professional antigen presenting cells. However, conventional CD4+ T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8+ T cells, which proliferate and become cytotoxic in response. CD4+</ ...[more]

PMID: 29147022

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Project description:Inflammation is a physiological state where immune cells evoke a response against detrimental insults. Finding a safe and effective treatment for inflammation associated diseases has been a challenge. In this regard, human mesenchymal stem cells (hMSC), exert immunomodulatory effects and have regenerative capacity making it a promising therapeutic option for resolution of acute and chronic inflammation. T cells play a critical role in inflammation and depending on their phenotype, they can stimulate or suppress inflammatory responses. However, the regulatory effects of hMSC on T cells and the underlying mechanisms are not fully elucidated. Most studies focused on activation, proliferation, and differentiation of T cells. Here, we further investigated memory formation and responsiveness of CD4+ T cells and their dynamics by immune-profiling and cytokine secretion analysis. Umbilical cord mesenchymal stem cells (UC-MSC) were co-cultured with either αCD3/CD28 beads, activated peripheral blood mononuclear cells (PBMC) or magnetically sorted CD4+ T cells. The mechanism of immune modulation of UC-MSC were investigated by comparing different modes of action; transwell, direct cell-cell contact, addition of UC-MSC conditioned medium or blockade of paracrine factor production by UC-MSC. We observed a differential effect of UC-MSC on CD4+ T cell activation and proliferation using PBMC or purified CD4+ T cell co-cultures. UC-MSC skewed the effector memory T cells into a central memory phenotype in both co-culture conditions. This effect on central memory formation was reversible, since UC-MSC primed central memory cells were still responsive after a second encounter with the same stimuli. The presence of both cell-cell contact and paracrine factors were necessary for the most pronounced immunomodulatory effect of UC-MSC on T cells. We found suggestive evidence for a partial role of IL-6 and TGFβ in the UC-MSC derived immunomodulatory function. Collectively, our data show that UC-MSCs clearly affect T cell activation, proliferation and maturation, depending on co-culture conditions for which both cell-cell contact and paracrine factors are needed.

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Conventional CD4⁺ T cells present bacterial antigens to induce cytotoxic and memory CD8⁺ T cell responses.

Publications

Conventional CD4<sup>+</sup> T cells present bacterial antigens to induce cytotoxic and memory CD8<sup>+</sup> T cell responses.

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Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses.

Publications

Conventional CD4&lt;sup&gt;+&lt;/sup&gt; T cells present bacterial antigens to induce cytotoxic and memory CD8&lt;sup&gt;+&lt;/sup&gt; T cell responses.

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Conventional CD4⁺ T cells present bacterial antigens to induce cytotoxic and memory CD8⁺ T cell responses.

Conventional CD4<sup>+</sup> T cells present bacterial antigens to induce cytotoxic and memory CD8<sup>+</sup> T cell responses.