Creating space: An antigen-independent, CpG-induced peripheral expansion of naive and memory T lymphocytes in a full T-cell compartment

Eduardo Davila, Maria G. Velez, Carrie J. Heppelmann, Esteban Celis

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Many of the mechanisms that govern T-cell homeostasis remain obscure. Here we report that repeated administration of synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG-ODN) into mice induces a systemic antigen-independent expansion of naive and memory T cells in a full T-cell compartment. Expansion of T cells was observed on both CD4+ and CD8+ T-cell subsets and was produced not by inducing the proliferation of the cells but by preventing their death. The antiapoptotic effects of CpG-ODN on T cells were observed against activation-induced death and growth factor withdrawal-mediated death. The ability of CpG-ODN to protect T cells from these forms of death was associated with the up-regulation of antiapoptotic gene products including c-FLIP, bcl-xL, and, to some extent, bcl-2. The effect of CpG-ODN on naive and memory T cells required the expression of CD28 and was not dependent on the presence of B lymphocytes, suggesting that other antigen-presenting cells that respond to CpG-ODN, such as dendritic cells, may provide antiapoptotic signals to T cells in an antigen-independent but CD28/B7-dependent fashion. The present findings suggest that CpG-ODN can disrupt normal T-cell homeostasis not by acting as a mitogen but by preventing T-cell death that normally takes place as a mechanism to maintain steady-state levels of T cells. These findings support a potential means to expeditiously replenish and maintain the peripheral lymphocyte population after severe immunodepletion such as that which occurs in HIV-infected individuals and individuals undergoing cytoablative therapies.

Original languageEnglish (US)
Pages (from-to)2537-2545
Number of pages9
JournalBlood
Volume100
Issue number7
DOIs
StatePublished - Oct 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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