Abundant expression of transforming growth factor-beta 1 and -beta 2 by Hodgkin's Reed-Sternberg cells and by reactive T lymphocytes in Hodgkin's disease.
The depressed cellular immunity observed in patients with Hodgkin's disease (HD) has been attributed to production of transforming growth factor (TGF)-beta or TGF-beta-like substances by Hodgkin's Reed-Sternberg (H-RS) cells. The TGF-beta produced by L-428 cells (an H-RS cell line) is a 130-kd molecular weight glycoprotein that apparently differs from the TGF-beta (molecular weight, 25 kd) produced by most lymphoid and hematopoietic cells. Among several distinct types of TGF-beta that have been purified, only TGF-beta 1 and TGF-beta 2 have thus far been identified in hematopoietic cells. By using monoclonal antibodies (1D11 and 3C7) and oligonucleotide probes specific for TGF-beta 1 and TGF-beta 2, were confirmed that a cultured H-RS cell line, KM-H2, can produce both TGF-beta types, whereas another line, HDLM-1, produces only TGF-beta 1. Despite the abundance of mRNA in both of these cells, only small amounts of TGF-beta activity were detected, probably because of rapid degradation of TGF-beta 1 mRNA by specific nuclease. No degraded TGF-beta 2 RNA products were observed in KM-H2 cells. The TGF-beta produced by both types of H-RS cells had a molecular weight of approximately 25 kd. In tissues expression of TGF-beta was observed in a small portion (30%) of H-RS cells in 16 of 20 cases examined. A large number of small to medium-sized lymphoid cells (T lymphocytes) in tissues involved by HD also were positive for TGF-beta. These results indicate that there is functional heterogeneity among H-RS cells, and that H-RS cells are not the only source of TGF-beta in tissues involved by HD. Hodgkin's Reed-Sternberg cells are known to secrete several other cytokines, including interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha. These cytokines could be responsible for the increased number of T lymphocytes in tissues involved by HD. Furthermore, T lymphocytes can respond to IL-1 and IL-6 secreted by H-RS cells by increasing their production of TGF-beta. Abundant expression of TGF-beta by T lymphocytes was not observed in lymphoid tissues other than those involved by HD.
Hsu
S M
SM
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock.
Lin
J
J
Xie
S S
SS
Hsu
P L
PL
Rich
S
S
D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D015870:Gene Expression / Q000235:genetics; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D012313:RNA / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D012313:RNA