Interleukin-7 Unveils Pathogen-Specific T Cells by Enhancing Antigen-Recall Responses

J Infect Dis. 2018 May 25;217(12):1997-2007. doi: 10.1093/infdis/jiy096.

Abstract

Background: Interleukin (IL)-7 promotes the generation, expansion, and survival of memory T cells. Previous mouse and human studies showed that IL-7 can support immune cell reconstitution in lymphopenic conditions, expand tumor-reactive T cells for adoptive immunotherapy, and enhance effector cytokine expression by autoreactive T cells. Whether pathogen-reactive T cells also benefit from IL-7 exposure remains unknown.

Methods: In this study, we investigated this issue in cultures of peripheral blood mononuclear cells (PBMCs) derived from patients infected with various endemic pathogens. After short-term exposure to IL-7, we measured PBMC responses to antigens derived from pathogens, such as Mycobacterium tuberculosis, Candida albicans, and cytomegalovirus, and to the superantigen Staphylococcus aureus enterotoxin B.

Results: We found that IL-7 favored the expansion and, in some instances, the uncovering of pathogen-reactive CD4 T cells, by promoting pathogen-specific interferon-γ, IL-2, and tumor necrosis factor recall responses.

Conclusions: Our findings indicate that IL-7 unveils and supports reactivation of pathogen-specific T cells with possible diagnostic, prognostic, and therapeutic significance of clinical value, especially in conditions of pathogen persistence and chronic infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Candida albicans / immunology
  • Candidiasis / immunology
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / immunology
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods
  • Interferon-gamma / immunology
  • Interleukin-2 / immunology
  • Interleukin-7 / immunology*
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Mycobacterium tuberculosis / immunology
  • Tuberculosis / immunology
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antigens
  • IL7 protein, human
  • Interleukin-2
  • Interleukin-7
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma