Creating space: an antigen-independent, CpG-induced peripheral expansion of naive and memory T lymphocytes in a full T-cell compartment.
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.
Davila
Eduardo
E
Department of Immunology and Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, USA.
Velez
Maria G
MG
Heppelmann
Carrie J
CJ
Celis
Esteban
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D005260:Female; D007156:Immunologic Memory / Q000187:drug effects*; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D015226:Dinucleoside Phosphates; D009838:Oligodeoxyribonucleotides; C015772:CpG dinucleotide