Infiltration of Th1 and Th2 lymphocytes around Hodgkin and Reed-Sternberg (H&RS) cells in Hodgkin disease: Relation with expression of CXC and CC chemokines on H&RS cells.
Hodgkin disease (HD) is characterized by the presence of Hodgkin and Reed-Sternberg cells (H&RS) and a prominent lymphocytic infiltration. Various CXC and CC chemokines [e.g., interferon-gamma-inducible protein-10 (IP10), monokine induced by interferon-gamma (MIG) and TARC] are expressed on H&RS cells. Our study was designed to investigate the expression of MIG, IP10 and TARC on H&RS cells and their relations on lymphocyte infiltration. Immunohistochemical staining was performed using antibodies for CXCR3 (a specific receptor for IP10 and MIG), which is characteristic of Th1 helper phenotype and CCR3, CCR4 and ST2, which are features of Th2 cells. We studied 15 cases of HD [lymphocyte predominance (LP) type, 2; mixed cellularity (MC) type, 6; and nodular sclerosis (NS) type, 7]. All 6 MC cases contained TARC-, IP10- and MIG-expressing H&RS cells, however only 2 of 5 NS cases contained TARC-expressing H&RS cells, 3 of 7 NS contained MIG-expressing H&RS cells and only 1 of 7 NS contained IP10-expressing H&RS cells. Neither of the 2 LP cases contained HR&S cells that expressed these chemokines. The chemokines were more frequently expressed by MC than by NS and LP types. IP10-, MIG- and TARC-positive HD cases contained higher numbers of Th2 lymphocytes (ST2- CCR3- or CCR4-positive lymphocytes), compared to IP10-, MIG- and TARC-negative HD cases (p < 0.05 or <0.5). The number of CXCR3 (MIG and IP10 receptor)-positive lymphocytes (Th1 lymphocytes) was not different between MIG- and IP10-positive and -negative HD. Lymphocytes surrounding MIG- and IP10-positive H&RS cells were more frequently CXCR3-positive, however, compared to MIG- and IP10-negative cases. The CCR4 (TARC receptor)-positive lymphocytes, surrounding H&RS cells, were minority and the surrounding lymphocytes were not different between TARC-positive and negative cases. Our results indicate that MIG, IP10 and TARC chemokines influenced the response of Th2 cells in HD. It is possible, however, that IP10 and MIG may locally influence Th1 cells via cell migration.
Ohshima
Koichi
K
Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan. ohshima@fukuoka-u.ac.jp
Tutiya
Takeshi
T
Yamaguchi
Takahiro
T
Suzuki
Keiko
K
Suzumiya
Junji
J
Kawasaki
Chika
C
Haraoka
Seiji
S
Kikuchi
Masahiro
M
D015704:CD4 Antigens / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D054414:Chemokine CCL17; D054370:Chemokine CXCL9; D019742:Chemokines, CC / Q000032:analysis / Q000096:biosynthesis; D019743:Chemokines, CXC / Q000032:analysis / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000235:genetics; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000032:analysis; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016753:Interleukin-10 / Q000032:analysis; D020382:Interleukin-18 / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D039102:Poly(A)-Binding Proteins; D011506:Proteins / Q000032:analysis; D012367:RNA, Viral / Q000235:genetics; D016601:RNA-Binding Proteins / Q000032:analysis; D054397:Receptors, CCR3; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine / Q000032:analysis; D018121:Receptors, Cytokine / Q000032:analysis; D016539:Reed-Sternberg Cells / Q000737:chemistry / Q000473:pathology* / Q000821:virology; D000074019:T-Cell Intracellular Antigen-1; D018417:Th1 Cells / Q000737:chemistry / Q000473:pathology*; D018418:Th2 Cells / Q000737:chemistry / Q000473:pathology*
C106230:CCL17 protein, human; C515350:CCR3 protein, human; C515354:CCR4 protein, human; D015704:CD4 Antigens; D019002:CD56 Antigen; D016827:CD8 Antigens; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054414:Chemokine CCL17; D054370:Chemokine CXCL9; D019742:Chemokines, CC; D019743:Chemokines, CXC; C079241:IL1RL1 protein, human; C104577:IP10-Mig receptor; D036341:Intercellular Signaling Peptides and Proteins; D000072179:Interleukin-1 Receptor-Like 1 Protein; D020382:Interleukin-18; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D054397:Receptors, CCR3; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D016753:Interleukin-10; D007371:Interferon-gamma