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Autophagy modulates CD4+ T-cell lineage recommitment upon pathogen infection

Cellular & Molecular Immunology volume 17, pages 682–683 (2020)Cite this article

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It is now well-established that antigen engagement and microenvironmental cytokine signals direct the functional plasticity of effector CD4+ T cells to shape the outcome of immune responses.5 In contrast, we have recently begun to appreciate that certain pathogens can reprogram the lineage commitment of effector CD4+ T cells to other T-cell lineages in the periphery. One example is that human immunodeficiency virus (HIV) can induce the generation of various lineage-intermediate populations, including CD4−CD8− and CD4+CD8+ T-cell subsets. Interestingly, one recent study shows that a unique population of MHC-II-restricted CD4−CD8+ T cells, which is derived from effector CD4+ T cells, displays strong proliferative capacity and antiviral function in HIV-infected patients.6 It is of great interest to understand the regulatory mechanisms governing the conversion of effector CD4+ T cells to this CD4−CD8+ T-cell subset, which may benefit the development of a novel strategy to reinvigorate antiviral responses in patients with HIV infection.

To explore how MHC-II-restricted CD4−CD8+ T cells are induced during pathogen infection, Robins et al. used the MHC-II-restricted antigen LLO190–205, a major epitope of Listeria monocytogenes that is recognized by CD4+ T cells, and transgenic TCR118 mice that contain CD4+ T cells specifically recognizing LLO190–205–MHC-II molecules. Upon in vitro stimulation, they found that TCR118 transgenic CD4+ T cells downregulate CD4 expression and concomitantly upregulate CD8 expression without altering the MHC-II restriction of LLO190-205. After in vivo L. monocytogenes infection, the authors show that a portion of antigen-experienced TCR118 transgenic CD4+ T cells give rise to MHC-II-restricted CD4−CD8+ T cells, reminiscent of the unique CD8+ T-cell subset observed in HIV-infected patients.6 The authors also observed a similar conversion of antigen-specific CD4+ T cells to MHC-II-restricted CD4−CD8+ T cells upon acute infection with lymphocytic choriomeningitis virus (LCMV). Moreover, these MHC-II-restricted CD4−CD8+ T cells express high levels of cytotoxic molecules granzymes A and B and perforin, as well as the cytokine IFNγ, suggesting that they are functionally similar to effector CD8+ T cells. These results indicate that the generation of MHC-II-restricted CD4−CD8+ T cells likely represents a general response to infectious microorganisms.

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Fig. 1: Autophagy limits the conversion of effector CD4+ T cells to MHC-II-restricted CD4−CD8+ T cells upon pathogen infection.

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Acknowledgements

The authors thank N. Chapman for the careful reading and editing of the paper.

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Authors and Affiliations

  1. Department of Pediatrics and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA

    Kai Yang

  2. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA

    Kai Yang

  3. Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Hongbo Chi

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Correspondence to Kai Yang or Hongbo Chi.

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Yang, K., Chi, H. Autophagy modulates CD4+ T-cell lineage recommitment upon pathogen infection. Cell Mol Immunol 17, 682–683 (2020). https://doi.org/10.1038/s41423-020-0368-0

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