The blood/brain barrier prevents the passive diffusion of proteins and metabolites from cerebral blood vessels into tissue spaces around neuronal and glial cells. To provide nutrients for these cells, transport mechanisms must exist and indeed have been demonstrated for metabolites. We now show that monoclonal antibodies against rat and human transferrin receptors label blood capillaries in the brain but not in other tissues. In the rat this labelling occurs after injection of antibody into the blood, thus the receptors seem to be accessible at the endothelial surface. It is possible that transferrin receptors are expressed on these cells to allow transport of transferrin (and thus iron) into brain tissues.

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Summary. Changes in the concentration of IgG^. IgC,, IgM, IgA and albumin in semm and mammary secretion were studied in 15 cows and 2 heifers before and after parturition. Concentrations of IgGj and IgC, in blood serum 3-5 weeks before parturition were 13-38 ± 0-75 and 10-08 ±: 0 39 mg/ml (means ± S.E.) respectively. In all animaLs tlie cfinc-entration of IgC, in serum decreased abruptly, usually by more than 50%, 2-3 weeks before parturition, and during the same period the concentrations of IgC2, IgM, IgA and albumin in seriun remained unchanged. Four weeks after parturition the concentration of IjiC, in serum had returned to values similar to tho.se observed prior to the abrupt fall.Five weeks before parturition the concentration of IgGj in mammary secretion was, on average, 11 times higher than that of IgC^. Highest concentrations of IgGj in secretion (113-89 rt 11-41 nig/ml) were obser^-ed 2-3 vi'eeks before parhirition in 16 of the 17 animals. The concentration of IgG., over the 5 weeks prior to parturition remained unchanged at levels of approx 30X of comparable values in seruui. Concei trations of IgM (11-8.^ ± 0-53) and IgA (3-80 it 0-20) in secretion collected prior to antl immediately afler parturition were, on average. 2 and 7 times higher respectively than those in serum."Hie sharp fall in the concentration of IgG, in serum in the absence of any suggestion of a concomitant decrease in IgGg concentration .strongly suggests that the degradation hypothesis proposed by Brambell (1958Brambell ( . 1966 for selective transfer of protein across epithelial membranes does not hold for the mammary gland of the cow. The results support an allernative hypothesis based on the existence of IgGj-specific receptor sites located on the basal or intercellular membrane of the glandular epitlieL'al cells.

Thymus-derived cells of the mouse, rat, and human can be divided, on the basis of differential expression of cell surface antigens, into phenotypically distinct subsets, and this phenotypic heterogeneity is correlated with functional differences (1-3). In the rat, the monoclonal antibody W3/25 (5) has been shown to label the T subset that contains helper cells for B cells (5) and cytotoxic T cells (6, 7) and also cells that mediate graft-versus-host (GvH) 1 reactivity (5). The monoclonal antibody MRC OX-8 labels the subset that contains suppressor and cytotoxic activities (2,6,8).In this paper a new monoclonal antibody MRC OX-22 is described that labels a subset of the W3/25 ÷ cells in the rat. Data are presented demonstrating that this phenotypic division is correlated with a functional one, with cells mediating help for B cells and those mediating GvH reactivity in different T cell subsets. Biochemical studies of the MRC OX-22 antigen demonstrate that it reacts with the high molecular weight form of the rat leukocyte-common antigen (L-CA). Materials and Methods RatsInbred rats from the specific pathogen-free unit at the MRC Cellular Immunology Unit were used. The strains were PVG/c (RTlC; Iglb), PVG-1 a (RTlC; Igla), and (PVG × DA)F~ (RTV × RTI"). PVG/c and PVG-I" are congenic strains that differ in their immunoglobulin light chain allotypes. Irradiations were performed using a 137Cs source at 94 rad/min (Gammacel; Atomic Energy of Canada).

The surface phenotypes (CD1, CD4, CD5, CD8, SBU-T19, MHC class I, MHC class II, and sIg) of cells in blood, lymph nodes, and lymph were determined to examine simultaneously the distribution of lymphocyte subsets circulating in blood, afferent lymph, and efferent lymph of a peripheral lymph node. Marked differences in the percentage of certain lymphocyte subsets were apparent within the compartments examined, suggesting that lymphocyte subsets leave the blood with differing efficiencies. Lymphocyte subsets also appeared to be extracted from the blood at different rates by lymph node as opposed to subcutaneous vascular endothelium. Endothelial cells in different vascular beds may express different numbers of molecules complementary to a set of migration-related cell surface molecules specific for each lymphocyte subset. Accordingly, the vascular endothelium would be the key factor in regulating nonrandom cell migration.

Human membrane cofactor protein (CD46) controls complement activation and when expressed sufficiently as a transgene protects xenografts against complement‐mediated rejection, as shown here using non‐immunosuppressed baboons and heterotopic CD46 transgenic pig kidney xenografts. This report is of a carefully engineered transgene that enables high‐level CD46 expression. A novel CD46 minigene was validated by transfection and production of a transgenic pig line. Pig lymphocytes were tested for resistance to antibody and complement‐mediated lysis, transgenic tissues were characterized for CD46 expression, and kidneys were transplanted to baboons without immunosuppression. Absorption of anti‐Galα(1,3)Gal epitope (anti‐GAL) serum antibodies was measured. Transgenic pigs expressed high levels of CD46 in all tissues, especially vascular endothelium, with stable expression through three generations that was readily monitored by flow cytometry of transgenic peripheral blood mononuclear cells (PBMC). Transgenic PBMC pre‐sensitized with antibody were highly resistant to human complement‐mediated lysis which readily lysed normal pig PBMC. Normal pig kidneys transplanted without cold ischemia into non‐immunosuppressed adult baboons survived a median of 3.5 h (n = 7) whereas transgenic grafts (n = 9), harvested at ∼24‐h intervals, were either macroscopically normal (at 29, 48 and 68 h) or showed limited macroscopic damage (median > 50 h). Microscopic assessment of transplanted transgenic kidneys showed only focal tubular infarcts with viable renal tissue elsewhere, no endothelial swelling or polymorph adherence and infiltration by lymphocytes beginning at 3 days. Coagulopathy was not a feature of the histology in four kidneys not rejected and assessed at 48 h or later after transplantation. Baboon anti‐GAL serum antibody titers were high before transplantation and, in one extensively analyzed recipient, reduced ∼8‐fold within 5.5 h. The data demonstrate that a single CD46 transgene controls hyperacute kidney graft rejection in untreated baboons despite the presence of antibody and complement deposition. The expression levels, tissue distribution and in vitro functional tests indicate highly efficient CD46 function, controlling both classical and alternative pathway complement activation, which suggests it might be the complement regulator of choice to protect xenografts.

Intraepithelial lymphocytes (IEL) of the uterus of non-pregnant sheep were analyzed by single- and two-color flow cytometry. Very few lymphocytes carrying classical B and T cell markers (CD5, surface immunoglobulin) were detected in the uterine epithelial cell suspensions and all IEL expressed the CD8 surface marker although with varying intensities. Three distinct subpopulations were identified including a major (46-56%) population of CD8+CD45R- gamma delta T cell receptor (TcR)-negative cells and approximately equal numbers of CD8+CD45R+ gamma delta TcR- and CD8+CD45R+ gamma delta TcR+ lymphocytes. The same three subpopulations were also present in the interplacentomal areas of the uterus of ewes at a late stage of pregnancy but there was a dramatic increase (60-70%) in the gamma delta TcR+ subpopulation. In addition, a pronounced increase in both size and granularity was observed in the IEL population of pregnant uteri and this was attributed to the gamma delta TcR+ cells. Light and electron microscopic examination of these gamma delta TcR+ IEL revealed an increase in metabolic activity and the formation of exceptionally large cytoplasmic granules and confirmed their restricted localization within the uterine epithelium close to the trophoblast. These results represent for the first time, a clear example of the activation of gamma delta TcR+ cells which is not associated with an ongoing disease process or infection. gamma delta TcR+ cells have recently been observed in the epithelium of the murine reproductive tract and were characterized by their unique homogeneous receptor structure. The present results indicate that these cells may play an important physiological role during pregnancy.

Monoclonal antibody has been obtained to the human complement control protein C3b inactivator after immunization of mice with the enzyme prepared by conventional methods. Antibody from ascitic fluid was purified and coupled to Sepharose-CL-4B to give a specific affinity column, which was used to isolate C3b inactivator from human serum in 70% yield. The product was characterized by size, chain structure, amino acid analysis and proteolytic activity.