Cytokine gene expression profile distinguishes CD4⁺/CD57⁺ T cells of the nodular lymphocyte predominance type of Hodgkin's lymphoma from their tonsillar counterparts

Abstract

Little is known about the cytokine profile of nodular lymphocyte predominance Hodgkin's lymphoma (NLPHL) and the significance of the characteristic rosetting CD4(+)/CD57(+) T cells. We analysed the T lymphocyte populations isolated from lymph node suspensions from five patients with NLPHL, two with follicular hyperplasia and progressive transformation of germinal centres (PTGC), three with classical Hodgkin's lymphoma (CHL) and five with hyperplasia of the tonsil. We sorted the T cells based on expression of CD3, CD4 and CD57 by flow cytometry and evaluated the cytokine mRNA profiles of the T cells with quantitative RT-PCR. NLPHL cases were as rich in T cells as the CHL cases, but all NLPHL cases had a much higher frequency of CD4(+)/CD57(+) T cells. In contrast to the CD4(+)/CD57(+) T cells from tonsils, IL2 and IL4 mRNAs were consistently absent from the CD4(+)/CD57(+) T cells of NLPHL. Even after stimulation, no IL4 transcripts could be detected in the CD4(+)/CD57(+) T cells of NLPHL. On the other hand, IFNgamma transcripts were elevated in NLPHL and PTGC T cell subsets as compared to tonsillar T cell subsets. IL13 mRNA was exclusively produced by the T cells of CHL cases, indicating that IL13 may be a key cytokine in CHL. In conclusion, elevated levels of CD4(+)/CD57(+) T cells are characteristic of NLPHL and these T cells display a distinct cytokine mRNA profile.

Hodgkin’s lymphoma associated T-cells exhibit a transcription factor profile consistent with distinct lymphoid compartments

“…29 However, we have recently reported that in contrast to their tonsillar counterparts, CD4 + /CD57 + T-cells of NLPHL do not express IL4 even after PMA-ionomycine activation. 2 This suggests that in NLPHL, c-Maf and MUM1/ IRF4 induced expression of IL4 is blocked. c-Maf also has a transforming ability, 30 and has been shown to function as an oncogene.…”

“…2 HL associated T H cells may represent an influx of T H cells from the circulation into the lymphoid tissues. In both types of HL, the T-cells rosetting around the neoplastic cells have a helper/inducer memory phenotype (CD4 + /CD45RO + ), express CD28 and display an activated phenotype with expression of CD69.…”

The CD4+CD26− T-cell population in classical Hodgkin's lymphoma displays a distinctive regulatory T-cell profile

“…[2][3][4][5] In return, these infiltrating cells produce cytokines that may contribute to proliferation and survival of the HRS cells. 6,7 The CD4 þ T cells surrounding the neoplastic cells in both cHL and NLPHL are CD45RO þ /CD45RAÀ/CD45RB dim , suggesting a memory Th2 phenotype. 8 Expression of several activation-associated surface markers, including CD38, CD69 and HLA class II, indicates that these CD4 þ T cells are activated.…”

Telomerase-specific GV1001 peptide vaccination fails to induce objective tumor response in patients with cutaneous T cell lymphoma

“…4A). These atypical T cells were identified as CD3 low CD4 + CD7 À CD10 + CD26 À CD57 + (data not shown), a phenotype characteristic of leukemic cells in CTCL [23,24]. They did not show a Treg phenotype (FoxP3 À CD25 low , data not shown).…”