NK cells could be in fact regulatory cells pushing maternal immune response toward a Th2 profile, beneficial for fetal survival, or toward a Th1 type of immune response, which acts in synergy. Modulation of TcR may represent a new mechanism for maternal-fetal tolerance.

Fetal thyroid goitres may reveal hormonal imbalance. This can jeopardize neurological development and fetal outcome even when early postnatal treatment is provided. We report a series of 11 goitres diagnosed antenatally in women with past or present thyroid disorders or discovered fortuitously on ultrasound scan. Fetuses presented with hyperthyroidism in three cases and hypothyroidism in eight. Hypothyroidism was iatrogenic in five cases, due to maternal anti‐thyroid drugs. Hyperthyroidism was induced by transplacental transfer of thyroid stimulating antibodies (TSHrab). Accurate diagnosis of fetal thyroid status was obtained by fetal blood sampling but this invasive method was deemed necessary only in four cases as maternal clinical and biological data and ultrasound signs provided sufficient information to infer the type of thyroid disorder in the remaining patients. Fetal therapy relied on reduction of maternal antithyroid medication and, in selected cases, intra‐amniotic injection of levothyroxin in hypothyroidism, and on administration of antithyroid drugs in hyperthyroidism. All newborns were healthy and none displayed consequences of severe thyroid imbalance. No caesarean section was performed for dystocia. Fetal thyroid goitres can be managed successfully with selected use of invasive diagnostic and therapeutic techniques. Copyright © 2000 John Wiley & Sons, Ltd.

PROBLEM: Allopregnancy induces specific transient tolerance to paternal grafts, and we know that a low molecular weight material (“filtrate”) present in a human placental supernatant can do so in vitro (specific unresponsiveness) as well as in vivo, such as when preventing grafl‐versus‐host reaction (GVH) produced by A cells injected into irradiated A × B F1s recipients. We also know by studies carried out using specific anti‐Vβ‐specific stimulation as well as secondary and primary mixed lymphocyte reaction in major histocompatibility complex (MHC) only incompatible combinations that the material acts by inducing T cell anergy rather than clonal deletion. We explored the mechanism of such an anergy, which we knew was not dependent on calcium fluxes, cyclic adenosine monophosphate (cAMP) levels, or PkC by studies of protein phosphorylation. Having observed in previous studies that expression of T cell reactivity (TcR) in anergic cells was enhanced, but that the numbers of cells expressing a given Vβ after specific stimulation in the presence of a filtrate was much higher than it should be, we monitored the receptor expression by fluorescence‐activated cell sorter (FACS). METHOD OF STUDY: We used short‐term stimulation of the T‐cell‐derived Jurkat E6‐1 cells by anti‐CD3 monoclonal antibody (mAb) or phorbol myristite acetate plus calcium ionophore in the presence or absence of human placental low molecular weight suppressor factor, followed by Western blotting. Transfer on nitrocellulose filters so as to allow the revelation of the phosphorylations was realized by means of a specific antiphosphotyrosin mAb. The final revelation was obtained by chemiluminescence. Similar experiments were performed on anti‐Vβ‐stimulated BALB/c splenocytes, as well as cyproflaxin‐treated cells, which are hyper‐responsive in cell proliferation assays in the presence of the filtrate. In parallel, cells that were stimulated by a specific anti‐Vβ and were rendered specifically anergic were studied by a specific anti‐Vβ and were rendered specifically anergic were studied for other TcR expression using an FACS and both fluorescein isothiocyanate (FITC) and phycoerythrin (PE)‐labelled, related and unrelated anti‐Vβ mAbs. RESULTS: The phosphorylation of the ζ chain homodimer quantitatively defective in filtrate‐treated, anti‐Vβ6‐stimulated splenocytes as well as in Jurkatt cells. In parallel, cells from cyproflaxin‐treated Jurkatt cells were showing enhanced phosphorylation of all bands. The labelling of filtrate‐treated anti‐Vβ6‐stimulated cells by an unrelated anti‐Vβ (anti‐Vβ8) showed double expression of Vβ chains. The percentage of cells expressing this unrelated Vβ (Vβ 8) was normal. CONCLUSIONS: T cell anergy induced by a filtrate is linked to defective phosphorylation of the ζ‐chain homodimer. The abnormal percentage of cells expressing TcR after filtrate treatment might be due to adsorption by unstimulated cells of soluble TcR Vβ‐chain, possibly as a result of excess synthesis followed by membrane protease cleavage, allowing release i...