Suppression of the primary cell-mediated immune response by human α1-fetoprotein in vitro

Auer, I. O.; Kress, Hans G.

doi:10.1016/0008-8749(77)90058-2

Cited by 50 publications

(13 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…During recent years it has been demonstrated that a-fetoprotein is the immunosuppressive agent responsible for these findings; other proteins and gestational hormones have had some suppressive activity in vitro, but only at high, unphysiological concentrations (29)(30)(31)(32)(33)(34)(35). Only isolated fetal a-fetoprotein has exerted an immunosuppressive effect on both the humoral and cellular immune functions, such as in vivo antibody synthesis in the rat and in vitro primary and secondary antibody response to sheep erythrocytes (23,36), B-and T-lymphocyte response to mitogens and antigens (27,(37)(38)(39)(40)(41), and generation of cytotoxic T cells (42). Immunofluoresoent studies have pointed to the presence of a-fetoprotein receptors on the surface of a subpopulation of T-cell lymphocytes in mice (43).…”

Section: Resultsmentioning

confidence: 99%

Inhibitory effect of alpha-fetoprotein on the binding of myasthenia gravis antibody to acetylcholine receptor.

Brenner¹,

Beyth²,

Abramsky³

1980

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The binding of myasthenia gravis antibody to acetylcholine receptor (AcChoR) as measured in vitro by radioimmunoassay with 125-labe ed a-bungarotoxin (a-BuTx), can be blocked by amniotic fluid, maternal serum, and umbilical cord serum. This inhibitory effect is due to a-fetoprotein present in high concentrations in amniotic fluid and serum, as shown by: (i) selective removal of several components from amniotic fluid and serum; (ih) selective addition of different components present in amniotic fluid and serum, including a-fetoprotein, to the radioimmunoassay; (iii) correlation between the inhibitory effect of both amniotic fluid and serum and between the amounts of a-fetoprotein they contain; (iv) blocking of the a-fetoprotein effect by pretreatment of the amniotic fluid with anti-a-fetoprotein anti'y. The inhibitory effect of a-fetoprotein in vitro suggests a similar effect in vivo in pregnant women with myasthenia gravis. This effect may explain in part the variability in the development of neonatal myasthenia gravis in the babies, due to transplacental transfer of maternal anti-AcChoR antibody, only after delivery and only in the minority of the cases. It also may explain the appearance of remissions in females with myasthenia gravis during the second and third trimesters of pregnancy. Similar phenomena observed during pregnancy in other autoimmune and immunopathogenic diseases also might be attributed to activity of a-fetoprotein.In studies from our laboratory (1, 2), we demonstrated that the in vitro binding of antibodies to acetylcholine receptor (AcChoR) from patients with myasthenia gravis to AcChoR antigen can be inhibited by: (i) human amniotic fluid obtained from healthy women during the second trimester; (Hi) serum obtained from healthy women during the second and third trimesters; and (iii) umbilical cord serum obtained after delivery from both healthy women and myasthenics. We suggested that a similar inhibitory effect in vivo on the binding of specific antibodies to AcChoR at the neuromuscular junction may occur during pregnancy in patients with myasthenia gravis. Because myasthenia gravis is an autoimmune disease caused by the immunopathologic effect of specific autoantibodies directed against AcChoR at the neuromuscular junction (3), such inhibitory effects may help to explain two phenomena observed in myasthenia gravis during pregnancy and after delivery: The occurrence of partial or complete remissions during the second and (especially) the third trimester, as well as exacerbations during the early postpartum period (4-8); and the appearance of transitory neonatal myasthenia gravis (NMG) in the newborn babies, due to placental transfer of maternal antibodies (9-11), only after birth and only in a minority of the cases (12, 13). This paper presents experimental data showing that the immunosuppressant a-fetoprotein, but not other components derived from both human amniotic fluid and human umbilical cord, is the factor inhibiting the binding of antibodies to AcChoR antigen present in the...

show abstract

Section: Resultsmentioning

confidence: 99%

Inhibitory effect of alpha-fetoprotein on the binding of myasthenia gravis antibody to acetylcholine receptor.

Brenner¹,

Beyth²,

Abramsky³

1980

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Before using AFP as a potential tumor rejection antigen in clinical studies, we examined its role on immune effector cells because immunosuppressive effects of AFP on immune cell function such as inhibition of antibody synthesis and T cell proliferation, induction of suppressor cells, as well as modulation of MHC class II expression and phagocytosis on macrophages has been postulated in the past [14][15][16][17][32][33][34]. Furthermore, an AFP specific receptor has been identified on human monocytes [25] and AFP was found to reduce the prostaglandin mediated production of TNF-a and IL-1b by monocytes [35].…”

Section: Discussionmentioning

confidence: 99%

“…However, until now the immunobiological function of AFP remains unclear. Some in vitro studies postulated an immunomodulating and immunosuppressing function of AFP [13][14][15][16][17][18][19][20][21][22][23][24]. The impact of serum AFP levels on immune cell functions in HCC patients is not known.…”

Section: Introductionmentioning

confidence: 99%

Immunoregulation of dendritic and T cells by alpha-fetoprotein in patients with hepatocellular carcinoma

Ritter

Ali

Grimm

et al. 2004

Journal of Hepatology

View full text Add to dashboard Cite

“…Previous studies have demonstrated inhibition ofnatural killer cell activity (8), the induction of T suppressor cells (9-1 1 ) the inhibition of mitogenic responses to PHA and Con A (12)(13)(14)(15), the inhibition of T cell proliferation to Ia determinants ( 16), decreased macrophage phagocytosis ( 17,18), and decreased macrophage Ia expression ( 19,20). Thus, the present study was undertaken to determine if the effects of AFP on immune function was mediated by a cell surface receptor on the immune recognition cell, the monocyte/macrophage.…”

Section: Introductionmentioning

confidence: 99%

Isolation and partial characterization of a specific alpha-fetoprotein receptor on human monocytes.

Suzuki

Zeng²,

Alpert³

1992

J. Clin. Invest.

View full text Add to dashboard Cite

Since a large body of data has suggested a significant role for alpha-fetoprotein (AFP) in the regulation of the immune response at a number of levels, we examined the possibility of a specific receptor for AFP on the immune recognition cell, the monocyte/macrophage. Microscopic autoradiography exhibited an obvious binding of AFP almost exclusively on human peripheral monocytes but not on lymphocytes. In a human monocyte cell line (U937) Scatchard plot analysis indicated the presence of two distinct AFP-specific binding sites with a Kd of 5 X 10-11 M, 49 binding sites per cell, and 2.5 X 10-7 M, 7,800 binding sites per cell. 125I-ASD-AFP, AFP-radiolabeled bifunctional photoactivatable thio-cleavable cross-linker, was used to isolate the AFP binding protein from U937 cells. After ultraviolet photoactivation, 125I-sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1,3'-dithiopropionate was covalently linked to the putative receptor. Autoradiography of SDS gradient PAGE under reducing conditions showed a major radiolabeled band at between 62 and 65 kD. To confirm the specificity of the finding, recombination of AFP with the isolated receptor was examined in artificially reconstituted membrane vesicles, which also resulted in a single band at 62-65 kD by SDS-PAGE autoradiography. From the data above, we concluded that human monocytes possess a specific AFP binding protein on the membrane, a putative receptor, which may be involved with the physiological regulation of the immune response. (J.

show abstract

Suppression of the primary cell-mediated immune response by human α1-fetoprotein in vitro

Cited by 50 publications

References 15 publications

Inhibitory effect of alpha-fetoprotein on the binding of myasthenia gravis antibody to acetylcholine receptor.

Inhibitory effect of alpha-fetoprotein on the binding of myasthenia gravis antibody to acetylcholine receptor.

Immunoregulation of dendritic and T cells by alpha-fetoprotein in patients with hepatocellular carcinoma

Isolation and partial characterization of a specific alpha-fetoprotein receptor on human monocytes.

Contact Info

Product

Resources

About