Naturally occurring PD-1+ memory phenotype CD8 T cells belong to nonconventional CD8 T cells and are cyclophosphamide-sensitive regulatory T cells

Koji Sakuraba, Kensuke Shibata, Yukihide Iwamoto, Yasunobu Yoshikai, Hisakata Yamada

Research output: Contribution to journalArticle

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Abstract

CD8 T cells expressing memory markers exist in naive mice and are thought to be of heterogeneous origin. It was recently reported that among such memory-phenotype (MP) CD8 T cells in naive mice, those expressing programmed death-1 (PD-1) had immune regulatory activity, but their origin and relationship with other regulatory CD8 T cell subsets remain unclear. In the current study, we examined detailed characteristics and functions of PD-1+ MP CD8 T cells in naive mice. Their expression pattern of surface molecules resembled that of exhausted CD8 T cells seen in chronic viral infection. However, PD-1+ MP CD8 T cells were detected from neonatal periods, even in the thymus; thus, they are naturally occurring. By analyzing bone marrow chimera mice in which β2-microglobulin-deficient mice were used as the recipients, it was revealed that PD-1+ MP CD8 T cells were positively selected by hematopoietic cells, indicating that they belong to nonconventional CD8 T cells. However, in contrast to majority of MP CD8 T cells, PD-1 + MP CD8 T cells were IL-15 independent. PD-1+ MP CD8 T cells showed the fastest cell cycling among various T cell subsets in naive mice, which was consistent with the highest sensitivity to cyclophosphamide (CP) treatment. Importantly, PD-1+ MP CD8 T cells were able to suppress delayed-type hypersensitivity response that was augmented by CP treatment. Taken together, our data indicate that the naturally occurring PD-1+ MP CD8 T cells in naive mice are a unique subset of nonconventional CD8 T cells and represent the CP-sensitive suppressor CD8 T cells.

Original languageEnglish
Pages (from-to)1560-1566
Number of pages7
JournalJournal of Immunology
Volume190
Issue number4
DOIs
Publication statusPublished - Feb 15 2013

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Regulatory T-Lymphocytes
Cyclophosphamide
T-Lymphocytes
Phenotype
T-Lymphocyte Subsets
Interleukin-15
Delayed Hypersensitivity
Virus Diseases
Thymus Gland
Cell Death
Bone Marrow

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Naturally occurring PD-1+ memory phenotype CD8 T cells belong to nonconventional CD8 T cells and are cyclophosphamide-sensitive regulatory T cells. / Sakuraba, Koji; Shibata, Kensuke; Iwamoto, Yukihide; Yoshikai, Yasunobu; Yamada, Hisakata.

In: Journal of Immunology, Vol. 190, No. 4, 15.02.2013, p. 1560-1566.

Research output: Contribution to journalArticle

Sakuraba, Koji ; Shibata, Kensuke ; Iwamoto, Yukihide ; Yoshikai, Yasunobu ; Yamada, Hisakata. / Naturally occurring PD-1+ memory phenotype CD8 T cells belong to nonconventional CD8 T cells and are cyclophosphamide-sensitive regulatory T cells. In: Journal of Immunology. 2013 ; Vol. 190, No. 4. pp. 1560-1566.
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