This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Albers, A. E. Articles by De Leo, A. B. Search for Related Content PubMed PubMed Citation Articles by Albers, A. E. Articles by De Leo, A. B.

Alterations in the T-Cell Receptor Variable ß Gene–Restricted Profile of CD8⁺ T Lymphocytes in the Peripheral Circulation of Patients with Squamous Cell Carcinoma of the Head and Neck

Authors' Affiliations: ¹ Divisions of Basic Research and Biostatistics, University of Pittsburgh Cancer Institute and Departments of ² Pathology, ³ Immunology, and ⁴ Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Requests for reprints: Albert B. De Leo, University of Pittsburgh Cancer Institute, Research Pavilion, Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA 15213. Phone: 412-623-3228; Fax: 412-1415; E-mail: deleo{at}imap.pitt.edu.

Purpose: Apoptosis of activated CD8⁺ T cells is often seen in tumor-infiltrating lymphocytes and circulating peripheral blood mononuclear cells (PBMC) in patients with squamous cell carcinoma of the head and neck (SCCHN). We investigated whether T-cell receptor (TCR) variable ß chain (Vß)–restricted T cells were more sensitive to apoptosis than non–TCR Vß-restricted T cells.

Experimental Design: Flow cytometry analysis with anti-TCR Vß antibodies was used to define expansions and contractions of Vß-restricted T cells in patients with SCCHN relative to normal donors. This staining was combined with Annexin V binding to indicate early T-cell apoptosis.

Results: The TCR Vß profiles of CD3⁺ T cells in tumor-infiltrating lymphocytes and PBMCs of patients with SCCHN were altered relative to controls, with one to five expansions and numerous contractions of TCR Vß-restricted T cells detected. These types of alterations were significantly greater in CD8⁺ than CD4⁺ T cells. Enhanced Annexin V binding to CD8⁺ T cells was evident in PBMCs obtained from all patients, with 3 of 13 showing preferential targeting for apoptosis of TCR Vß-restricted T cells.

Conclusions: TCR Vß profiles of CD8⁺ T cells were altered in patients with SCCHN relative to normal controls. This may reflect increased apoptosis of expanded or contracted CD8⁺ T cells, which define the TCR Vß profile of antigen-responsive T-cell populations in patients with cancer.