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The Journal of Immunology, 2006, 176: 6340-6346.
Copyright © 2006 by The American Association of Immunologists

Influence of CD4+CD25+ Regulatory T Cells on Low/High-Avidity CD4+ T Cells following Peptide Vaccination1

Hiroyoshi Nishikawa*, Feng Qian{dagger}, Takemasa Tsuji*, Gerd Ritter*, Lloyd J. Old*, Sacha Gnjatic2,3,* and Kunle Odunsi2,3,{dagger}

* Ludwig Institute for Cancer Research, New York Branch, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and {dagger} Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263

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-1157–170 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-1157–170 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.




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