OX40 costimulatory signals potentiate the memory commitment of effector CD8+ T cells

Seyed Fazlollah Mousavi, Pejman Soroosh, Takeshi Takahashi, Yasunobu Yoshikai, Hao Shen, Leo Lefrançois, Jannie Borst, Kazuo Sugamura, Naoto Ishii

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

Abstract

A T cell costimulatory molecule, OX40, contributes to T cell expansion, survival, and cytokine production. Although several roles for OX40 in CD8 + T cell responses to tumors and viral infection have been shown, the precise function of these signals in the generation of memory CD8+ T cells remains to be elucidated. To address this, we examined the generation and maintenance of memory CD8+ T cells during infection with Listeria monocytogenes in the presence and absence of OX40 signaling. We used the expression of killer cell lectin-like receptor G1 (KLRG1), a recently reported marker, to distinguish between short-lived effector and memory precursor effector T cells (MPECs). Although OX40 was dispensable for the generation of effector T cells in general, the lack of OX40 signals significantly reduced the number and proportion of KLRG1low MPECs, and, subsequently, markedly impaired the generation of memory CD8+ T cells. Moreover, memory T cells that were generated in the absence of OX40 signals in a host animal did not show self-renewal in a second host, suggesting that OX40 is important for the maintenance of memory T cells. Additional experiments making use of an inhibitory mAb against the OX40 ligand demonstrated that OX40 signals are essential during priming, not only for the survival of KLRG1low MPECs, but also for their self-renewing ability, both of which contribute to the homeostasis of memory CD8+ T cells.

Original languageEnglish
Pages (from-to)5990-6001
Number of pages12
JournalJournal of Immunology
Volume181
Issue number9
DOIs
Publication statusPublished - 2008 Nov 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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