Interleukin-21 induces short-lived effector CD8+ T cells but does not inhibit their exhaustion after Mycobacterium bovis BCG infection in mice

Naoto Noguchi, Risa Nakamura, Shinya Hatano, Hisakata Yamada, Xun Sun, Naoya Oohara, Yasunobu Yoshikai

Research output: Contribution to journalArticle

Abstract

Interleukin 21 (IL-21) is a pleiotropic common cytokine receptor γ chain cytokine that promotes the effector functions of NK cells and CD8+ T cells and inhibits CD8+ T cell exhaustion during chronic infection. We found that the absolute number of short-lived effector CD8+ T cells (SLECs) (KLRG1high CD127low) decreased significantly in IL-21 receptor-deficient (IL-21R-/-) mice during Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection. Early effector CD8+ T cells (EECs) (KLRG1low CD127low) were normally generated in IL-21R-/- mice after infection. Exhausted CD8+ T cells (PD-1high KLRG1low) were also normally generated in IL-21R-/- mice after infection. Mixed bone marrow (BM) chimera and transfer experiments showed that IL-21R on CD8+ T cells was essential for the proliferation of EECs, allowing them to differentiate into SLECs after BCG infection. On the other hand, the number of SLECs increased significantly after infection with recombinant BCG (rBCG) that secreted an antigen 85B (Ag85B)-IL-21 fusion protein (rBCG-Ag85B-IL-21), but the number of exhausted CD8+ T cells did not change after rBCG-Ag85B-IL-21 infection. These results suggest that IL-21 signaling drives the differentiation of SLECs from EECs but does not inhibit the exhaustion of CD8+ T cells following BCG infection in mice.

Original languageEnglish
Article numbere00147-18
JournalInfection and Immunity
Volume86
Issue number8
DOIs
Publication statusPublished - Aug 1 2018

Fingerprint

Mycobacterium bovis
Bacillus
T-Lymphocytes
Infection
Interleukin-21 Receptors
Antigens
interleukin-21
Recombinant Fusion Proteins
Cytokine Receptors
Natural Killer Cells
Bone Marrow
Cytokines

Keywords

  • CD8 T cells
  • EECs
  • IL-21R
  • PD-1
  • SLECs

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Interleukin-21 induces short-lived effector CD8+ T cells but does not inhibit their exhaustion after Mycobacterium bovis BCG infection in mice. / Noguchi, Naoto; Nakamura, Risa; Hatano, Shinya; Yamada, Hisakata; Sun, Xun; Oohara, Naoya; Yoshikai, Yasunobu.

In: Infection and Immunity, Vol. 86, No. 8, e00147-18, 01.08.2018.

Research output: Contribution to journalArticle

Noguchi, Naoto ; Nakamura, Risa ; Hatano, Shinya ; Yamada, Hisakata ; Sun, Xun ; Oohara, Naoya ; Yoshikai, Yasunobu. / Interleukin-21 induces short-lived effector CD8+ T cells but does not inhibit their exhaustion after Mycobacterium bovis BCG infection in mice. In: Infection and Immunity. 2018 ; Vol. 86, No. 8.
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