Induction of regulatory T cell-resistant helper CD4+ T cells by bacterial vector Journal Article
| Authors: | Nishikawa, H.; Tsuji, T.; Jager, E.; Briones, G.; Ritter, G.; Old, L. J.; Galán, J. E.; Shiku, H.; Gnjatic, S. |
| Article Title: | Induction of regulatory T cell-resistant helper CD4+ T cells by bacterial vector |
| Abstract: | Salmonella typhimurium engineered to deliver cancer/testis antigen NY-ESO-1 through type III secretion (S typhimurium-NY-ESO-1) was shown to be an efficient cancer vaccine construct in mice and to stimulate NY-ESO-1-specific CD8+/CD4+ T cells in vitro in patients with cancer with NY-ESO-1 spontaneous immunity. e also showed that individuals without spontaneous immunity to NY-ESO-1 had specific CD4+ T-cell precursors with high avidity to NY-ESO-1 under tight control by CD4+CD25 + regulatory T (Treg) cells. We now found that in healthy donors and patients with melanoma without NY-ESO-1 spontaneous immunity, S typhimurium-NY-ESO-1 elicits CD4+ T helper 1 (Th1) cells in vitro recognizing naturally processed antigen from these high-avidity NY-ESO-1-specific naive precursors. In contrast to peptide stimulation, induction of specific Th1 cells with S typhimurium-NY-ESO-1 did not require in vitro depletion of CD4+CD25+ Treg cells, and this prevailing effect was partially blocked by disruption of interleukin-6 or glucocorticoid-nduced TNF receptor (GITR) signals. Furthermore, S typhimurium-induced Th1 cells had higher GITR expression than peptide-nduced Th1 cells and were resistant to suppression by CD4+CD25+ Treg cells in a GITR-dependent fashion. We propose that S typhimurium-NY-ESO-1 induces antigenspecific T-cell responses that are resistant to suppression by CD4+CD25+ Treg cells. © 2008 by The American Society of Hematology. |
| Keywords: | signal transduction; controlled study; protein expression; human cell; sensitivity and specificity; cells, cultured; melanoma; membrane proteins; cell differentiation; in vitro study; genetic vectors; cd4+ cd25+ t lymphocyte; regulatory t lymphocyte; lymphocyte activation; antigens, neoplasm; ny eso 1 antigen; cd4+ t lymphocyte; interleukin 6; interleukin-6; immunity; t-lymphocytes, helper-inducer; th1 cell; glucocorticoid induced tumor necrosis factor receptor; t lymphocyte activation; interleukin-2 receptor alpha subunit; receptors, tumor necrosis factor; receptors, nerve growth factor; salmonella typhimurium; bacterium carrier |
| Journal Title: | Blood |
| Volume: | 111 |
| Issue: | 3 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2008-02-01 |
| Start Page: | 1404 |
| End Page: | 1412 |
| Language: | English |
| DOI: | 10.1182/blood-2007-09-113761 |
| PUBMED: | 17986662 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 18" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus" |
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