Anti-idiotypic T cells suppress rejection of renal allografts in rats

Kidney allografts between inbred rats differing at the major histocompatibility complex (MHC) are normally rejected, usually within 10 to 12 days. In many strain combinations, however, permanent graft acceptance can be induced by either immunological enhancement or a short course of immunosuppressive chemotherapy. In both cases, prolonged graft survival is accompanied by the appearance in the spleen of a population of suppressor cells. When transferred to a syngeneic host, these cells abrogate or strikingly diminish the rejection response elicited by a renal allograft of the same genotype as the original kidney donor. We have now examined the properties of these suppressor cells and have detected a subpopulation that proliferates in vitro when stimulated by irradiated syngeneic T blasts reactive to MHC alloantigens of the kidney donor strain. Comparable proliferation, however, is not induced either by syngeneic blasts reactive to a third strain or by polyclonal syngeneic blasts. These results support the hypothesis that this subpopulation is anti-idiotypic, with specificity for the idiotypes carried by syngeneic T cells stimulated by the kidney allograft. Such anti-idiotypic cells could function as suppressors.     

Analysis of T-cell subsets in rejection of Kb mutant skin allografts differing at class I MHC

The T-cell subpopulations which initiate and mediate tissue allograft rejection remain controversial. In the present study we attempted to identify the phenotype and function of the T-cell subset(s) primarily responsible for the rejection of skin allografts differing at a single class I locus in the major histocompatibility complex (MHC). We found that the rejection rates by B6 mice (H-2b) of four different class I mutant (Kbm) skin allografts form a distinct hierarchy. This hierarchy correlates strikingly and uniquely with the relative precursor frequencies of Lyt2+ interleukin-2-secreting T-helper cells reactive against the various Kbm mutants. To investigate the role of Lyt2+ T cells in the rejection of class I-disparate skin allografts directly, H-2b nude mice were engrafted with Kbm skin allografts and then reconstituted with L3T4+ or Lyt2+ T-cell subpopulations from syngeneic H-2b mice. Lyt2+ T cells were observed to be both necessary and sufficient for the rejection of class I-disparate Kbm skin allografts, whereas L3T4+ T cells were neither necessary nor sufficient. These results identify the Lyt2+ interleukin-2-secreting T-cell subset as the critical cell type determining the rejection rate of class I-disparate Kbm skin allografts.     

Facilitation of voltage-gated ion channels in frog neuroglia by nerve impulses

The functions of glial cells in the nervous system are not well defined, with the exception of myelin production by oligodendrocytes, uptake of amino-acid synaptic transmitters, and a contribution to extracellular potassium homeostasis. Neuroglia have receptors for neurotransmitters which may be involved in neuron-glia interactions. Recent studies have demonstrated voltage-gated ion channels in glial membranes. In a study of the optic nerve of the frog, small areas of the surface were examined with the loose patch-clamp method, and voltage-gated Na+ and K+ channels, presumably located in the membranes of the astrocytes forming the glia limitans, were identified. We now report that nerve impulses in the axons of the frog optic nerve transiently alter the properties of the voltage-dependent membrane channels of the surface glial cells (astrocytes), a demonstration of a new form of neuron-glia interaction.     

Met- and Leu-enkephalin immunoreactivity in separate neurones.

A pair of pentapeptides, Met- and Leu-enkephalin were recently isolated from brain tissue. The two peptides seem to represent endogenous opiate receptor ligands and have by immunocytochemical and radioimmunoassay studies been shown to occur in an extensive system of cerebral and peripheral nerves. The relative proportions between Met- and Leu-enkephalin varies between different brain regions and also between different species, suggesting the existence of separate populations of Met- and Leu-enkephalin nerves. Until now, however, immunocytochemistry has given no support for this notion. We report here evidence of separate populations of Met- and Leu-enkephalin nerves.     

Evidence for coexistence of dopamine and CCK in meso-limbic neurones

Vanderhaeghen et al. reported the occurrence of gastrin-like immunoreactivity in the mammalian brain. Subsequent studies have revealed that this immunoreactivity corresponded mainly to the COOH-terminal octapeptide of cholecystokinin (CCK-8), which has a COOH-terminal pentapeptide identical to gastrin. Also, two peptides resembling the NH- and the COOH-terminal tetrapeptide fragments of CCK-8 are present in the central nervous system (CNS). Using COOH-terminal-specific antisera raised to gastrin and/or CCK, the distribution of CCK neurones has been described with immunohistochemical techniques. Although high numbers of cells and nerve terminals are found in cortical areas, the CCK systems are also present in most other parts of the brain and spinal cord. In the CNS, true gastrin molecules, gastrin-17 and gastrin-34 have been located only in the neurohypophysis, hypothalamus and occasionally in the medulla oblongata (unpublished results). We describe here the occurrence of peptides in meso-limbic dopamine neurones in the rat brain. Evidence has also been obtained that mesencephalic dopamine neurones in the human brain contain similar peptides.     

First visualization of glutamate and GABA in neurones by immunocytochemistry

Immunocytochemical methods for peptides and serotonin have greatly advanced the study of neurones in which these substances are likely to be transmitters. Such direct techniques have not so far been available for the amino acid transmitter candidates. We report here the selective immunocytochemical visualization of the putative transmitters glutamate (Glu) and gamma-aminobutyrate (GABA) by the use of antibodies raised against the amino acids coupled to bovine serum albumin (BSA) with glutaraldehyde (GA). The tissue localizations of Glu-like and GABA-like immunoreactivities (Glu-LI and GABA-LI) matched those of specific uptake sites for Glu and GABA, and, in the case of GABA-LI, also that of the specific marker enzyme glutamic acid decarboxylase (GAD). Thus, GABA-LI was located in what are believed to be GABAergic inhibitory neurones, whereas Glu-LI was concentrated in excitatory, possibly glutamatergic neurones. Preliminary electron microscopic observations suggest that the transmitter amino acids are significantly concentrated in synaptic vesicles.     

Vernier acuity of neurones in cat visual cortex

The ability of human observers to detect Vernier breaks of as little as 5 s arc has been termed hyperacuity as this distance is substantially less than the angular separation of the bars of the highest spatial frequency of grating (approximately 1 arc min) that can be detected. Although the visual cortex is a likely candidate for the location of detectors involved in this performance, it is not known whether there are cells sensitive enough to detect deviations from co-linearity that are small compared with their spatial resolution (defined in terms of the highest spatial frequency that the cell can detect). We report here the results of physiological experiments on single units in area 17 of the cat visual cortex in which we studied the effect of introducing a Vernier break into a bar stimulus moved across the receptive field of the cell at a constant velocity. Our results show that the responses of most simple and complex cells are significantly reduced by the introduction of a Vernier break that is substantially smaller than the spatial resolution of the cell. The most sensitive cells in our sample could discriminate Vernier offsets of 3-6 arc min with a reliability of approximately 70%. This was much smaller than their spatial resolution, which was in the range 25-30 arc min. We interpret these results in terms of mechanisms that could underly the orientation selectivity of cortical neurones and suggest how our results relate to human Vernier acuity.