Bystander central memory but not effector memory CD8+ T cells suppress allograft rejection

Ni Wan, Hehua Dai, Tao Wang, Yolonda Moore, Xin Xiao Zheng, Zhenhua Dai

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Memory T cells respond faster and more vigorously than their naive counterparts and are critical for adaptive immunity. However, it is unknown whether and how memory T cells react in the face of irrelevant Ags. It is generally accepted that bystander memory T cells are neutral in immune responsiveness. In this study, we present the first evidence that bystander central memory (TCM), but not effector memory (TEM), CD8+ T cells suppress allograft rejection as well as T cell proliferation in the draining lymph nodes (DLN) of recipient mice. Both bystander TCM and naive T cells, but fewer TEM cells, migrated to DLN, whereas TCM cells exhibited faster turnover than their naive counterparts, suggesting that bystander TCM cells have an advantage over their naive counterparts in suppression. However, bystander TEM cells migrated to inflammatory graft sites, but not DLN, and yet failed to exert their suppression. These findings indicate that bystander memory T cells need to migrate to lymph nodes to exert their suppression by inhibiting responder T cell activation or homeostatic proliferation. Moreover, the suppression mediated by bystander TCM cells was largely dependent on IL-15, as IL-15 was required for their homeostatic proliferation and T CM-mediated suppression of allograft rejection. This suppression also required the presence of TGFβ1, as TCM cells expressed TGFβ1 while neutralizing TGFβ1 abolished their suppression. Thus, bystander TCM, but not TEM, CD8+ T cells are potent suppressors rather than bystanders. This new finding will have an impact on cellular immunology and may have clinic implications for tolerance induction.

Original languageEnglish
Pages (from-to)113-121
Number of pages9
JournalJournal of Immunology
Volume180
Issue number1
StatePublished - 1 Jan 2008
Externally publishedYes

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