¹Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Correspondence: Dr A van den Berg, PhD, Department of Pathology and Laboratory Medicine, University Medical Center Groningen, PO Box 30.001, Hanzeplein 1, Groningen 9700 RB, The Netherlands. E-mail: a.van.den.berg@path.umcg.nl

Received 23 November 2007; Revised 5 February 2008; Accepted 14 February 2008; Published online 24 March 2008.

Abstract

Little is known about the gene expression profile and significance of the rosetting CD4+CD26- T cells in classical Hodgkin's lymphoma (cHL). To characterize these T cells, CD4+CD26- and CD4+CD26+ T-cell populations were sorted from lymph node (LN) cell suspensions from nodular sclerosis HL (NSHL) and reactive LNs. mRNA profiles of stimulated and resting cell subsets were evaluated with quantitative RT-PCR for 46 genes. We observed a higher percentage of CD4+CD26- T cells in NSHL than in reactive LNs. The resting CD4+CD26- T cells in NSHL showed higher mRNA levels of CD25, CTLA4, OX40 and CCR4 compared with in LNs, supporting a regulatory T-cell (Treg) type, and this was validated by immunohistochemistry. Moreover, these cells showed low or no expression of the Th1- or Th2-related cytokines IL-2, IFN-, IL-13, IL-12B, IL-4, and IL-5, and the chemoattractant receptor CRTH2. Besides Tregs, Th17 cells may exist in NSHL based on the significantly higher IL-17 mRNA level for both T-cell populations in NSHL. Upon stimulation in vitro, lack of upregulation of mRNA levels of most cytokine genes indicated an anergic character for the CD4+CD26- T-cell subset. Anergy fits with the Treg profile of these cells, probably explaining the immunosuppressive mechanism involved in NSHL.