Chin Med J (Taipei) 1998;61:S121.

Hodgkin's Disease - Unique Cytokine and Cytokine Receptor Profile Distinguished From That of Non-Hodgkin's Lymphomas

Su-Ming Hsu, Pei-Ling Hsu

Department of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan and University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

Abstract

In cultures, and in tissues as well, Hodgkin's and Reed-Sternberg (H-RS) cells are known to express a variety of cytokines, including IL-1, -5, -6, -7, -8, -9, TNF-alpha, TNF-beta, GM-CSF, M-CSF, TGF-beta, CD70, CD80, and CD86. Various numbers of H-RS cells may express cytokine receptors (R), such as CD30, CD40, IL-2R (CD25/CD122), IL-6R (CD126), IL-7R (CD127), IL-18R, TNF-R (CD 120), TGF-beta-R (CD105/endoglin), M-CSF-R (CD115), and SCF-R (CD117/ c-kit receptor). All of these cytokines and cytokine receptors are implicated in the growth regulation of H-RS cells, the histopathologic alterations in tissues, and the clinical manifestations in patients with Hodgkin's disease (HD). Many of these cytokines or cytokine receptors also play an important role in the pathogenesis of other types of lymphomas. In this presentation, we describe the cytokine or cytokine-receptor expression that is diacritic for H-RS cells. The identification of such unique cytokine-cytokine receptor interactions is likely to explain the biologic property that distinguishes HD from other types of lymphomas. These interactions include those of CD30L-CD30, CD40L-CD40, CD70-CD27, CD80/CD86-CD28, SCF-CD117, IL-9-IL9R, IL-7-IL-7R, and IL-18-IL-18R. The H-RS cells express IL-9 and two cytokine receptors, CD30 and CD117, which are observed infrequently in NHLs. Although IL-7 expression is not restricted to H-RS cells, the expression of IL-7 in conjunction with IL-9 and/or CD117 may be regarded as unique for HD because of an unusual combination and a synergistic activity among these cytokines. The expression of CD70 and CD80/CD86 (as cytokines) may exert a unique effect in HD because of intimate contact between H-RS cells and CD27/CD28-positive T cells. The expression of these co- stimulators (CD70 and CD80/CD86) and other adhesion/costimulator molecules such as CD54 and CD58, along with the secretion of soluble cytokines such as IL- 1, IL-6, IL-7, or TNFs by H-RS cells, could result in the profound T-cell proliferation often seen in lymph nodes involved by HD. On the other hand, the expression of CD30L, CD40L, and IL-18 by surrounding T cells may affect the proliferation of H-RS cells. The cytokine-cytokine receptor interaction between H-RS cells and T cells via direct cell-cell contact is bi-directional, a situation not commonly seen in NHLs.

[Chin Med J (Taipei) 1998;61:S121.]