Characterization of an immunosuppressive factor secreted by a human trophoblast-derived choriocarcinoma cell line. 1995

L Krishnan, and S Sad, and R Raghupathy
Immunogenetics Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.

Factors and cells of placental origin have been considered to be important in mediating local active immunosuppression that regulates maternal immune reactivity to aid fetal survival. In this context, we investigated the immunosuppressive capabilities of supernatants from human trophoblast-derived choriocarcinoma cell lines (HCS). We have previously reported the inhibitory effects of HCS on proliferative responses of T-lymphocytes both in vitro and in vivo (L. Krishnan, E. Menu, G. Chaouat, G. P. Talwar, and R. Raghupathy, Cell. Immunol. 138, 113, 1991; L. Krishnan, R. Kinsky, G. Chaouat, G.P. Talwar, and R. Raghupathy, Cell. Immunol. 150, 376, 1993). We now show that HCS also suppresses LPS-induced proliferation of murine lymphocytes but does not inhibit the constitutive proliferation of lymphoma cell lines and B cell hybridomas indicating that HCS has no inhibitory effects on terminally differentiated or transformed cells. Furthermore, we have succeeded in isolating and partially characterizing the HCS-derived suppressor factor (HCSf) from culture supernatants of a human choriocarcinoma cell line JEG-3. Purification of the factor has been accomplished by sequential fractionation on anion-exchange, gel filtration, and reverse-phase HPLC columns. The suppressor factor is a low-molecular-weight compound in the range of 5-6 kDa, composed predominantly of hydrophilic amino acids. Protease digestion of the factor revealed that the peptide moiety in HCSf is important for its inhibitory activity. HCSf mediates a dose-dependent suppression of proliferative responses of both human and murine lymphocytes.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008970 Molecular Weight The sum of the weight of all the atoms in a molecule. Molecular Weights,Weight, Molecular,Weights, Molecular
D010450 Endopeptidases A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS. Endopeptidase,Peptide Peptidohydrolases
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D002241 Carbohydrates A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. The largest class of organic compounds, including STARCH; GLYCOGEN; CELLULOSE; POLYSACCHARIDES; and simple MONOSACCHARIDES. Carbohydrate
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002822 Choriocarcinoma A malignant metastatic form of trophoblastic tumors. Unlike the HYDATIDIFORM MOLE, choriocarcinoma contains no CHORIONIC VILLI but rather sheets of undifferentiated cytotrophoblasts and syncytiotrophoblasts (TROPHOBLASTS). It is characterized by the large amounts of CHORIONIC GONADOTROPIN produced. Tissue origins can be determined by DNA analyses: placental (fetal) origin or non-placental origin (CHORIOCARCINOMA, NON-GESTATIONAL). Choriocarcinomas
D005260 Female Females

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