Autophagy modulates cd4+ t-cell lineage recommitment upon pathogen infection

Access through your institution Buy or subscribe 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

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local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Singer,

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paper. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pediatrics and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN,

USA Kai Yang * Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA Kai Yang * Department of Immunology, St. Jude Children’s Research

Hospital, Memphis, TN, USA Hongbo Chi Authors * Kai Yang View author publications You can also search for this author inPubMed Google Scholar * Hongbo Chi View author publications You can

also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to Kai Yang or Hongbo Chi. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing

interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 03 January 2020 * Accepted: 03 January 2020 * Published: 11 February

2020 * Issue Date: July 2020 * DOI: https://doi.org/10.1038/s41423-020-0368-0 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable

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