Expression of CD1c, CD1d and Presence of Invariant NKT Cells in Hodgkin Lymphoma.

Hodgkin lymphoma (HL) is a B-cell neoplasm characterized by a minority of neoplastic cells, the so-called Hodgkin and Reed-Sternberg (HRS) cells. The HRS cells are located within an extensive infiltrate of reactive cells, including T cells, B cells, plasma cells, stromal cells, eosinophils and macrophages. CD1 molecules are non-classical MHC I-like molecules that present lipid antigens to T cells, triggering a specific immune response. Of the five CD1 isoforms (CD1a, CD1b, CD1c, CD1d and CD1e) expressed in human tissue, only CD1c and CD1d are expressed in B cells. The T cell receptors (TCRs) of T cells that recognize CD1c are indistinguishable from those that recognize MHC class I or II complexes. In contrast, CD1d presents lipid antigens to invariant Natural Killer T cells (iNKT cells), which are characterized by the expression of a semi-invariant Vα24Jα18 chain plus a limited set of β chains. CD4⁻ and CD4⁺ iNKT cells were demonstrated as two distinct functional subsets in terms of cytokine production and cytotoxic activation. Immunoregulatory CD1 restricted T cells have been implicated in the pathogenesis of many cancers, but its role in HL is still unknown. In this study, we analyzed the expression of CD1c, CD1d and presence of iNKT cells in HL.

Expression of CD1c and CD1d was determined by immunocytochemistry in four HL cell lines KMH2, L1236, L428 and U-HO1. CD1c and CD1d expression in both HRS cells and reactive cells was studied in 46 HL patient tissues by immunohistochemistry. Cell suspensions of ten HL cases were studied for the presence of iNKT cells using monoclonal antibodies against human iNKT cell (clone 6B11) and TCR Vβ11 (clone C21) by flow cytometry. The percentage of CD4⁺ iNKT cells was determined in the gated iNKT cell population.

Cytoplasmic CD1d expression was found in four HL cell lines and membranous CD1d expression was found in KMH2 and L1236. CD1c expression was negative in all four HL cell lines. CD1d expression was detected in HRS cells in 46% (21/46) of the HL cases. No correlation was observed between CD1d expression and presence of EBV in HRS cells. In contrast, CD1c expression was negative in HRS cells in all HL cases. Both CD1c and CD1d were detected in reactive cells in all HL cases albeit at varying frequencies. The mean percentage of CD1d restricted iNKT cells was 4% (range 0.8-8%) in HL cell suspensions irrespective of CD1d expression status in HRS cells. In reactive lymph node (RLN) the mean percentage of iNKT cells was also 4% (range 0.4-7%). Approximately half of the iNKT cells were CD4⁺ in both HL and RLN cell suspensions.

Expression of CD1d was found in four HL cell lines and in HRS cells of ∼50% of the HL cases. In HL cell suspensions, about 4% (range 0.8-8%) of the reactive background cells were iNKT cells.

No relevant conflicts of interest to declare.