Immonobiological function of trophoblast to circulating maternal IgG antibodies; antibodies to blood group antigen and HLA

29

o r d i n a r i l y s u p p r e s s e d b y the p u r i f i e d IgG. In c y t o t o x i c i t y t e s t , the purified IgG showed cytotoxic activities against paternal T and/or B lymphocytes. The purified IgG which had been absorbed w i t h p o o l e d p l a t e l e t s s h o w e d a n t i - D R a c t i v i t i e s to p a n e l l e d B cells. F r o m t h e s e r e s u l t s , t h e p l a c e n t a l IgG is s u p p o s e d to b i n d the p a t e r n a l h i s t 0 c o m p a t i b i l i t y a n t i g e n s o n the p l a c e n t a a n d b l o c k the c e l l m e d i a t e d i m m u n i t y a g a i n s t t h e c o n c e p t u s .

IMMUNOREGULATORY ROLE OF PLACENTAL GLYCOPROTEINS NITY. Gopal S. Gupta, Radslav G. Kinsky, Guy Andr4 Voisin. C.I.P.I.Ex. (U 23 INSERM, LA Ci-Bernard, H6p. St-Antoine: 75571 PARIS Cedex

IN CELLULAR AND HUMORAL IMMUHuynh Thien Duc, and 289 CNRS, C 16 Ass 12 France

Suppressor cells and enhancing antibodies specific for paternal transplantation antigens are preferentially produced during murine pregnancy with respect to cytctoxic cells and antibodies~ at variance with artificial transplantations. It is suggested that substances present in the placenta are playing a role in this immunodeviated response. Glass homogenized placental soluble extracts from CBA mice were fractionated on a Con A-Sepharose column into 10 fractions under various conditions of pH and temperature~ Their effect was investigated on alloantibody immune responses as wel I as on the response to Sa I (A/J) allo grafts. CBA mice were immunized with 10v A/J spleen cells along with 200 ;g of placental glycoprotein fractions and blood was sampled on days 5, 10 and 15. On day 16 mice were grafted with Sa I cells. Two groups of mice received either nothing (normal controls) or only spleen cells (immune controls) Fresh PBS whole soluble extracts were immunosuppressive at the humoral level but did not significantly modify the rejection rate of Sa I. On the other hand most of the fractions induced delayed rejection of Sa I, but only fractions eluted by 0 6 M ~methyl D-glucoside at pH 7.1 and 4 ° C seemed to reduce the level of cytotoxic antibodies. Moreover the deoxycholate solubilized placental pellet caused a significantly delayed rejection of Sa I, suppression of cytotoxic antibodies and higher levels of anaphylactic antibodies. These results suggest that placental immunosuppressive factors are mainly glycoproteins which may be linked with the successful outcome of pregnancy. These factors a*'e bound to cell membranes (where they are presumed to exert a maximum local effect) and released into the circulation (where they induce a systemic effect). Immonobiological function of trophoblast tO_circulating maternal IgG a n t i b o d i e s ; a n t i b o d i e s to b l o o d g r o u p a n t i g e n a n d HLA.

Department

M. M o r i s a d a , S . K a w a k a m i of OB/GYN, Keio University,

and R.Iizuka Tokyo, Japan

Human ABO antigens are widely distributed on all tissues. These antigens are not only red cell antigens, but also major transplantation antigens. Three pregnant women of blood type O,Rh positive, s h o w e d v e r y h i g h a n t i - A a n d B a n t i b o d i e s t h r o u g h the a n t e n a t a l A n t i g l o b u l i n test. I g G a n t i b o d i e s o f t h e s e c a s e s w e r e r e c o g n i z e d b y I g G a b s o r p t i o n test, a n t i g l o b u l i n p o s i t i v e t e s t a f t e r r e m o v a l of IgM antibodies using 2-Mercaptoethanol and Neutr AB-Dase methods. Sera of these patients were eluted by DEAE cellulose column a n d IgG f r a c t i o n s w e r e o b t a i n e d . T h e s e I g G s h o w e d p o s i t i v e A n t i g l o b u l i n test. C l i n i C a l s e q u e n c e o f t h e s e p a t i e n t s a r e a s f o l l o w s , o n e n e w b o r n o f b l o o d t y p e A a n d t w o o f t y p e B w e r e born, o n e n e o n a t e s h o w e d H e m o l i t i c D i s e a s e o f N e w b o r n (HDN) a f t e r d e l i v e r y , o n the c o n t r a r y , t w o o t h e r c a s e s no H D N a n d d i r e c t A n t i g l Q b u l i n t e s t was negative. Previously, we observed that HLA antiDoales were

30 d e t e c t e d among p r e g n a n t w o m e n but these a n t i b o d i e s were not observed in coad blood of newborn. To explain these contradiction,i.e., p r e s e n c e of IgG a n t i b o d i e s to A,B and HLA antigens in maternal c i r c u l a t i o n and negative i m m u n o l o g i c a l hazadous effect to fetus, we propose again our h y p o t h e s i s (published in 1976) "Immunobiological function of the s v n c v t i o t r o p h o b l a s t " in w h i c h we d e s c r i v e d "the fetal a n t i g e n - m a t e r n a l a n t i b o d y complexes formation and r e s o l u t i o n system inside the s y n c y t i o t r o p h o b l a s t " .

IMMUNOSUPPRESSIVE T CELL CIRCUIT INDUCED BY TROPHOBLAST-DERIVED Fc-BINDING PROTEIN Noboru Matsuzaki, Kiichiro Itoh , Yutaka Izumi, Hiromi Fujiwara, and Toshiyuki Hamaoka. Inst. for Cancer Res., Osaka Univ. Med. Sch., Fukushima-ku, 553, Japan. The question of how semi-allogeneic fetus and placenta can survive uninterrupted in maternal environment is not yet answered. One of the plausible mechanisms is that trophoblast may escape from maternal immunological attack by re]easing putative immunosuppressive factors. To analize such immunological mechanisms, we used human choriocarcinoma ceil lines as a model and found an intriguing immunosuppressive T cell c i r c u i t induced by trophoblast-derived factor. In culture supernates of various choriocarcinoma cell lines, two d i s t i n c t factors were present: One was immunosuppressive factor and the other was antigen non-specific lymphocyte proliferating factor which was easily inactivated by u l t r a v i o l e t irradiation. The immunosuppressive factor was found to have a strong a f f i n i t y to the Fc portion of IgG but not of F(a~)zof IgG, suggesting this factor to be Fc receptor-like molecule. The Fc recepLor-like molecule with similar property was also detected in supernate of primary culture of normal trophoblast. Interestingly, this immunosuppressive factor induced suppressor T cells in human and mouse immune system, which, in turn, produce a potent immunosuppresive T cell factor with d i s t i n c t immunological property from o r i g i n a l l y added trophoblast-derived factor. Thus, the immunosuppressive factor derived from trophoblast may play an important role in damping maternal semiallograft rejection through activation of suppressor T cell pathway. PURIFICATION AND CHARACTERIZATIONOF IMMUNOSUPPRESSIVE FACTOR DERIVED FROMHUMANTROPHOBLASTAND MALIGNANTCELLS. Kiichiro Itoh, Noboru Matsuzaki, Yutaka Izumi, Hiromi Fujiwara, and Toshiyuki Hamaoka. Inst. for Cancer Res., Osaka Univ. Med. Sch., Fukushima-ku, 553, Japan. Immunologists have long questioned how semi-allogeneic mammalian embryo survive uninterrupted in contact with genetically different maternal environment. Cancer researchers also have held that tumor cells mimic a condition of fetalism. Information leading to knowledge of how fetal ceils such as trophoblast and i t s malignant transformed choriocarcinoma survive may open new avenues to cope with cancer. Standing on these basic notions, we have endeavored to establish an experimental system to detect such biologically important immunosuppressive factor from trophoblast, and tried to correlate i t with immunosuppressive factors from various cancer cell lines. Results of our recent analyses revealed that human trophoblast and various cancer cell lines including choriocarcinoma release mutually related immunosuppressive factors. In this report, u t i l i z i n g the supernate of HSB-2 (human T cell leukemia) as an example, we tried to purify and characterize such immunosuppressive factor. The HSB-2