Authors: | Nishikawa, H.; Qian, F.; Tsuji, T.; Ritter, G.; Old, L. J.; Gnjatic, S.; Odunsi, K. |
Article Title: | Influence of CD4+CD25+ regulatory T cells on low/high-avidity CD4+ T cells following peptide vaccination |
Abstract: | We have recently reported that NY-ESO-1-specific naive CD4+ T cell precursors exist in most individuals but are suppressed by CD4 +CD25+ regulatory T cells (Tregs), while memory CD4 + T cell effectors against NY-ESO-1 are found only in cancer patients with spontaneous Ab responses to NY-ESO-1. In this study, we have analyzed mechanisms of CD4+ T cell induction following peptide vaccination in relation to susceptibility to Tregs. Specific HLA-DP4-restricted CD4+ T cell responses were elicited after vaccination with NY-ESO-1 157-170 peptide (emulsified in IFA) in patients with NY-ESO-1-expressing epithelial ovarian cancer. These vaccine-induced CD4 + T cells were detectable from effector/memory populations without requirement for in vitro CD4+CD25+ T cell depletion. However, they were only able to recognize NY-ESO-1157-170 peptide but not naturally processed NY-ESO-1 protein and had much lower avidity compared with NY-ESO-1-specific pre-existing naive CD4+CD25- T cell precursors or spontaneously induced CD4+ T cell effectors of cancer patients with NY-ESO-1 Ab. We propose that vaccination with NY-ESO-1 157-170 peptide recruits low-avidity T cells with low sensitivity to Tregs and fails to modulate the suppressive effect of Tregs on high-avidity NY-ESO-1-specific T cell precursors. Copyright © 2006 by The American Association of Immunologists, Inc. |
Keywords: | controlled study; unclassified drug; human cell; cancer patient; cells, cultured; ovary cancer; membrane proteins; cell differentiation; peptide; cd4+ cd25+ t lymphocyte; regulatory t lymphocyte; antigen presentation; amino acid sequence; molecular sequence data; antigens, neoplasm; t-lymphocytes, regulatory; ny eso 1 antigen; antibody response; cd4+ t lymphocyte; vaccination; stem cells; effector cell; t cell depletion; epitopes, t-lymphocyte; cell adhesion; t lymphocyte activation; vaccines, subunit; immunologic memory; memory t lymphocyte; hla dp antigen; hla dp4 antigen; seryllysyllysylmethionyltryptophylisoleucylthreonylglutaminylcysteinylpheny lalanyllysylprolylvalylphenylalanyllysylarginylglutaminylproline |
Journal Title: | Journal of Immunology |
Volume: | 176 |
Issue: | 10 |
ISSN: | 0022-1767 |
Publisher: | The American Association of Immunologists, Inc |
Date Published: | 2006-05-15 |
Start Page: | 6340 |
End Page: | 6346 |
Language: | English |
PUBMED: | 16670346 |
PROVIDER: | scopus |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 28" - "Export Date: 4 June 2012" - "CODEN: JOIMA" - "Source: Scopus" |