Expression of CCL28 by Reed-Sternberg cells defines a major subtype of classical Hodgkin's disease with frequent infiltration of eosinophils and/or plasma cells.
Classical Hodgkin's disease (HD) is characterized by rare neoplastic Hodgkin and Reed-Sternberg (H-RS) cells within abundant reactive cellular backgrounds. In most cases, H-RS cells originate from the B-cell lineage, but their immunophenotypes are unusual. Here we newly found frequent expression of chemokine receptors CXCR6 and CCR10 and their respective ligands CXCL16 and CCL28 in HD-derived cell lines. CCR10 is known to be selectively expressed by plasma cells, whereas CCL28 attracts eosinophils via CCR3 and plasma cells via CCR10 and CCR3. Therefore, we examined their expression in HD tissues by immunohistochemistry. We found that H-RS cells in 15 of 19 cases were positive for CCL28. Among them, seven cases were also positive for CCR10, suggesting a potential autocrine effect. In situ hybridization confirmed the expression of CCL28 mRNA in H-RS cells. The CCL28 positivity in H-RS cells did not significantly correlate with that of LMP-1, CCL17, CCL22, or CCL11. However, it significantly correlated with the background accumulation of eosinophils, plasma cells, and CCR10+ cells. Thus, the production of CCL28 by H-RS cells may play a major role in tissue accumulation of eosinophils and/or plasma cells in classical HD. The frequent expression of CCR10 in H-RS cells themselves also supports their close relationship to plasma cells.
Department of Hematology, Nephrology, and Rheumatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
Hitoshi
H
Hanamoto
Takashi
T
Nakayama
Hajime
H
Miyazato
Sumio
S
Takegawa
Kunio
K
Hieshima
Yoichi
Y
Tatsumi
Akihisa
A
Kanamaru
Osamu
O
Yoshie
D000293:Adolescent; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D000075743:Chemokine CXCL16; D018925:Chemokines / Q000096:biosynthesis* / Q000276:immunology*; D019742:Chemokines, CC; D019743:Chemokines, CXC / Q000096:biosynthesis; D002633:Chemotaxis; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006689:Hodgkin Disease / Q000145:classification* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D008875:Middle Aged; D010950:Plasma Cells / Q000473:pathology; D054447:Receptors, CCR10; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000096:biosynthesis; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011991:Receptors, Virus / Q000096:biosynthesis; D016539:Reed-Sternberg Cells / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C414047:CCL28 protein, human; C515706:CCR10 protein, human; C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D017931:DNA Primers; D008565:Membrane Proteins; D054447:Receptors, CCR10; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011991:Receptors, Virus