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.
The transport of calcium ions (Ca(2+)) to the cytosol is essential for immunoreceptor signaling, regulating lymphocyte differentiation, activation, and effector function. Increases in cytosolic-free Ca(2+) concentrations are thought to be mediated through two interconnected and complementary mechanisms: the release of endoplasmic reticulum Ca(2+) "stores" and "store-operated" Ca(2+) entry via plasma membrane channels. However, the identity of molecular components conducting Ca(2+) currents within developing and mature T cells is unclear. Here, we have demonstrated that the L-type "voltage-dependent" Ca(2+) channel Ca(V)1.4 plays a cell-intrinsic role in the function, development, and survival of naive T cells. Plasma membrane Ca(V)1.4 was found to be essential for modulation of intracellular Ca(2+) stores and T cell receptor (TCR)-induced rises in cytosolic-free Ca(2+), impacting activation of Ras-extracellular signal-regulated kinase (ERK) and nuclear factor of activated T cells (NFAT) pathways. Collectively, these studies revealed that Ca(V)1.4 functions in controlling naive T cell homeostasis and antigen-driven T cell immune responses.
All the specific radiosensitive cells required for the induction and expression of the primary antibody response to sheep erythrocytes in the rat are normally present among the small lymphocytes in thoracic duct lymph (1, 2). Experiments with radiation chimeras have now made it clear that the activity of thoracic duct cells in this response is due to the presence in rat lymph of two populations of small lymphocytes, one derived from the thymus (T lymphocytes) 1 and the other derived from the bone marrow without thymic influence (B lymphocytes).2 Thymus-marrow collaboration in the rat, first reported by Johnston and Wilson (3), is similar to that originally described in mice by Mitchell and Miller (4).The present work extends the earlier findings on radiation chimeras by demonstrating that thymus-and marrow-derived small ]ymphocytes are present in the thoracic duct lymph of normal rats, and establishes three criteria by which the two populations may be distinguished. These are: (a) a marked deficiency of uridine incorporation in vitro by B lymphocytes relative to T lymphocytes; (b) a small difference in the rate of sedimentation; (c) a physiological segregation after transfusion into the blood, into clearly distinct zones within the spleen, lymph nodes, and Peyer's patches, which define the areas through which the two cell populations recirculate. Materials and MelhodsAnimals.--Young adult male and female rats of the inbred HO and AO strains were used in this study.Collection from the Tlzoracic Dztct of Pure Marrow-Derived Lymphocy/es and Artificial Mixtures of ~Iarrow-Derived and T Lymphacyles.--Adult rats were thymectomized, irradiated with 1000 rads from a 6°Co source, and then injected intravenously with 10 7 bone marrow cells from 1 Abbreviations used in this" paper: B ]ymphocytes, peripheral bone marrow-derived small lymphocytes; DAB, Dulbecco's A q-B (buffered salt solution); D/E/FCS, fetal calf serum in Dulbecco's modified Eagle's medium; PBS, phosphate-buffered saline; T Iymphocytes, peripheral thymus-derived small ]ymphocytes.2 Scott, D. W., and J. C. Howard. Collaboration between thymus-derived and marrowderived thoracic duct lymphocytes in the hemolysin response of rat.
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