No abstract

Lymph nodes with Hodgkin disease (HD)harbor few neoplastic cells in a marked leukocytic infiltrate. Since chemokines are likely to be involved in the recruitment of these leukocytes, the expression of potentially relevant chemokines and chemokine receptors were studied in lymph nodes from 24 patients with HD and in 5 control lymph nodes. The expression of regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1␣, and MIP-1␤ was analyzed by in situ hybridization and that of CCR3 and CCR5 by immunohistochemistry and flow cytometry. It was found that, overall, the expression of all 4 chemokines was markedly enhanced, but the cellular source was different. RANTES was expressed almost exclusively by T cells whereas the expression of MCP-1, MIP-1␣, and MIP-1␤ was confined largely to macrophages. In control lymph nodes, chemokine expression was low, with the exception of MIP-1␣ in macrophages. CCR3 and CCR5 were highly expressed in T cells of HD involved but not of control lymph nodes. CCR3 was equally distributed in CD4 ؉ and CD8 ؉ cells, but CCR5 was associated largely with CD4 ؉ cells. In HD lymph nodes, CCR3 and CCR5 were also expressed in B cells, which normally do not express these receptors. All these chemokines and receptors studied, by contrast, were absent in the neoplastic cells. It was concluded that chemokines are involved in the formation of the HD nonneoplastic leukocytic infiltrate. Expression of CCR3 and CCR5 appears to be characteristic of HD, but the roles of these receptors' up-regulation for the disease process remain unclear. IntroductionHodgkin disease (HD) is characterized by the presence of few neoplastic mononuclear Hodgkin cells and polynuclear ReedSternberg (H-RS) cells surrounded by a dense nonneoplastic leukocytic infiltrate consisting of lymphocytes, plasma cells, granulocytes, and macrophages. 1 In the nodular sclerosis (NS) and mixed cellularity (MC) subtypes, CD4 ϩ T cells are particularly frequent in this infiltrate. They almost exclusively have the CD45RO ϩ and CD45RB ϩ phenotype and are in a state of activation that, based on their cytokine expression, appears to be related to a T-helper 2 (T H 2)-mediated immune response. [2][3][4] H-RS cells express various cell surface molecules, including CD58 (intercellular adhesion molecule 1), CD40, CD30, and CD80 (B7-1) as well as major histocompatibility complex class II molecules, 5,4 and produce numerous cytokines, such as interleukin (IL)-1, IL-5, IL-6, IL-9, macrophage-colony stimulating factor, tumor necrosis factor (TNF)-␣, 6 and IL-13, 7 that may have multiple effects on the surrounding leukocytes.Few studies have addressed the role of chemokines in HD. For instance, the IL-8 gene expressed by reactive cells in lymph nodes involved by HD is related to the presence of neutrophilic granulocytes. 8 Studies based mainly on reverse-transcription polymerase chain reaction technology show that HD tissues also express higher levels of inducible prot...