Immune escape mechanisms in Hodgkin's disease

Abstract

Background: The nodular sclerosis and mixed cellularity subtypes of Hodgkin's disease are histologically characterised by a small population of neoplastic cells, the so-called Reed-Sternberg cells and their mononuclear variants (RS cells) and an extensive admixture of other cell types including lymphocytes, plasma cells, eosinophils, and histiocytes. The nature of this infiltrate is largely known, but the mechanisms and functional effects are not. The small lymphocytes immediately surrounding the RS cells are mostly CD4+ T cells that express early activation markers. The absence of prominent specific cytotoxic T cell or natural killer (NK) cell populations seems to argue against a Th1-type response, whereas the sometimes prominent admixture of plasma cells and eosinophils is suggestive of a Th2-type response. Enrichment of the CD4 T-cell population may result from selective influx of CD4 T cells or from selective depletion of CD8 cells and NK cells. Results and discussion: The T cells surrounding RS cells have an immuno-phenotype and cytokine production capability consistent with a Th2-type response. RS cells express several members of the TNF receptor family such as the FAS ligand (CD95L) that may induce apoptosis of activated, FAS expressing, CD8+ T cells and NK cells. The RS cells also produce TGFβ and interleukin-10 that may downmodulate the Th1 response. In addition, the Reed-Sternberg cells produce the chemokine TARC that could lead to the specific attraction of a Th2 T- cell subset. Conclusion: RS cells have several mechanisms that may allow it to escape an effective immune response. The relative contributions of each of these and other potential mechanisms are not yet known.