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Prepublished online as a Blood First Edition Paper on May 13, 2002; DOI 10.1182/blood-2002-02-0401.
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Blood, 1 October 2002, Vol. 100, No. 7, pp. 2537-2545
IMMUNOBIOLOGY
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, and
Esteban Celis
From the Department of Immunology and Mayo Graduate
School, Mayo Clinic, Rochester, MN.
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.
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