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Conversion of effector CD4+ T cells to a CD8+ MHC II-recognizing lineage.

Publication ,  Journal Article
Robins, E; Zheng, M; Ni, Q; Liu, S; Liang, C; Zhang, B; Guo, J; Zhuang, Y; He, Y-W; Zhu, P; Wan, Y; Li, Q-J
Published in: Cell Mol Immunol
January 2021

CD4+ and CD8+ T cells are dichotomous lineages in adaptive immunity. While conventionally viewed as distinct fates that are fixed after thymic development, accumulating evidence indicates that these two populations can exhibit significant lineage plasticity, particularly upon TCR-mediated activation. We define a novel CD4-CD8αβ+ MHC II-recognizing population generated by lineage conversion from effector CD4+ T cells. CD4-CD8αβ+ effector T cells downregulated the expression of T helper cell-associated costimulatory molecules and increased the expression of cytotoxic T lymphocyte-associated cytotoxic molecules. This shift in functional potential corresponded with a CD8+-lineage skewed transcriptional profile. TCRβ repertoire sequencing and in vivo genetic lineage tracing in acutely infected wild-type mice demonstrated that CD4-CD8αβ+ effector T cells arise from fundamental lineage reprogramming of bona fide effector CD4+ T cells. Impairing autophagy via functional deletion of the initiating kinase Vps34 or the downstream enzyme Atg7 enhanced the generation of this cell population. These findings suggest that effector CD4+ T cells can exhibit a previously unreported degree of skewing towards the CD8+ T cell lineage, which may point towards a novel direction for HIV vaccine design.

Duke Scholars

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Published In

Cell Mol Immunol

DOI

EISSN

2042-0226

Publication Date

January 2021

Volume

18

Issue

1

Start / End Page

150 / 161

Location

China

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Immunology
  • Histocompatibility Antigens Class II
  • Female
  • Class III Phosphatidylinositol 3-Kinases
  • Cell Lineage
 

Citation

APA
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Robins, E., Zheng, M., Ni, Q., Liu, S., Liang, C., Zhang, B., … Li, Q.-J. (2021). Conversion of effector CD4+ T cells to a CD8+ MHC II-recognizing lineage. Cell Mol Immunol, 18(1), 150–161. https://doi.org/10.1038/s41423-019-0347-5
Robins, Elizabeth, Ming Zheng, Qingshan Ni, Siqi Liu, Chen Liang, Baojun Zhang, Jian Guo, et al. “Conversion of effector CD4+ T cells to a CD8+ MHC II-recognizing lineage.Cell Mol Immunol 18, no. 1 (January 2021): 150–61. https://doi.org/10.1038/s41423-019-0347-5.
Robins E, Zheng M, Ni Q, Liu S, Liang C, Zhang B, et al. Conversion of effector CD4+ T cells to a CD8+ MHC II-recognizing lineage. Cell Mol Immunol. 2021 Jan;18(1):150–61.
Robins, Elizabeth, et al. “Conversion of effector CD4+ T cells to a CD8+ MHC II-recognizing lineage.Cell Mol Immunol, vol. 18, no. 1, Jan. 2021, pp. 150–61. Pubmed, doi:10.1038/s41423-019-0347-5.
Robins E, Zheng M, Ni Q, Liu S, Liang C, Zhang B, Guo J, Zhuang Y, He Y-W, Zhu P, Wan Y, Li Q-J. Conversion of effector CD4+ T cells to a CD8+ MHC II-recognizing lineage. Cell Mol Immunol. 2021 Jan;18(1):150–161.

Published In

Cell Mol Immunol

DOI

EISSN

2042-0226

Publication Date

January 2021

Volume

18

Issue

1

Start / End Page

150 / 161

Location

China

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Immunology
  • Histocompatibility Antigens Class II
  • Female
  • Class III Phosphatidylinositol 3-Kinases
  • Cell Lineage