Introduction: Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) are surrounded by a majority of infiltrating reactive cells, which mainly consists of CD4+ T cells. These T cells express several activation associated surface markers but lack expression of the T cell co-stimulatory molecule CD26. Little is known about the significance of these rosetting CD4+CD26- T cells.

Methods: To characterize these T cells, CD4+CD26- and CD4+CD26+ T cells were sorted from lymph node cell suspensions from 7 cHL and 5 reactive lymph nodes (LN). Of 5 HL cases and 3 lymph nodes, parts of the cells were stimulated with PMA/ionomycin to get activated T cell subsets. mRNA profiles of activated and non-activated T cell populations were evaluated with quantitative RT-PCR for 46 selected genes.

Results: We observed a higher percentage of CD4+CD26- T cells in cHL compared to reactive LN. For the non-activated T cell subsets, CD4+CD26- T cells in cHL showed higher mRNA levels of IL2RA, CTLA4, TNFRSF4 and CCR4 compared to LN. Moreover, these cells displayed low or no expression of the Th1 or Th2 related cytokines IL2, IFNγ, IL13, IL12B, IL4, IL5 and the chemoattractant receptor GPR44. Overall, the profiling results support a regulatory T (Treg) cell type for the CD4+CD26- T cells in cHL. Besides Tregs, Th17 cells may exist in cHL based on the significantly higher IL17 mRNA level for both the CD26- and CD26+ T cells in cHL than in LN. Upon activation, the lack of up-regulation of mRNA levels of most cytokine genes (IFNγ, IL2, IL8, IL21, IL17, IL13, IL12A and IL4) indicated an anergic character for the CD4+CD26− subset in cHL.

Conclusion: A high proportion of CD4+CD26− T cells is characteristic for cHL. No evidence for a Th1 or Th2 cell type is found for these cells but they display a regulatory T cell phenotype. Anergy fits with the regulatory T cell profile of these cells, probably explaining the immunosuppressive mechanism involved in cHL.

Author notes

Disclosure: No relevant conflicts of interest to declare.