Monoclonal antibodies against human T lymphocytes label Purkinje neurones of many species

Garson, Jeremy A.; Beverley, Peter C. L.; Coakham, Hugh B.; Harper, Ei

doi:10.1038/298375a0

Cited by 193 publications

(31 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the first demonstration of the Thy-1 antigen expressed in the immune and nervous systems of the mouse (Reif and Allen, 1964) antigenic sharing in man has been described repeatedly (Garson et al, 1982;Hauser et al, 1983;Schuller-Petrovic et al, 1983;Budka and Majdic, 1985). At present the significance of the cross-reactivity between nervous elements and lymphocytes has not been clarified, but there is increasing evidence that shared antigens may be involved in the pathogenesis of immune-mediated neurologic diseases.…”

Section: Introductionmentioning

confidence: 99%

Expression of the CD6 T lymphocyte differentiation antigen in normal human brain☆

Mayer

Funke²,

Seed

et al. 1990

Journal of Neuroimmunology

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Expression of the CD6 T lymphocyte differentiation antigen in normal human brain☆

Mayer

Funke²,

Seed

et al. 1990

Journal of Neuroimmunology

View full text Add to dashboard Cite

“…Its neuronal circuit and development are well understood (3, 4), and several markers have already been found that specifically bind to Purkinje cells (5)(6)(7) and granule cells (8). Methods for culturing Purkinje cells (5) and granule cells (8)(9)(10) have also been established.…”

mentioning

confidence: 99%

Voltage-gated and synaptic currents in rat Purkinje cells in dissociated cell cultures.

Hirano¹,

Ohmori²

1986

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The electrical properties of rat Purkinje cells and synapses from granule cells were studied in dissociated cell cultures. To identify the cells we used an immunohistochemical method and recorded voltage-gated and synaptic currents with the patch-clamp technique (the whole-cell mode). Cultured Purkinje cells generated action potentials similar to those recorded from in vitro slices or in vivo preparations. Early Na, late Ca inward current, and K outward currents were distinguished by ion substitution under voltage clamp. We also recorded spontaneous synaptic currents in Purkinje cells cultured with granule cells. These synaptic currents reversed direction at the membrane potential of 2.5 mV, which was similar to currents induced by L-glutamate. Therefore, these are most likely excitatory synaptic currents from granule cells. Since these properties of Purkinje cells examined here are similar to those in situ, the cells in dissociated cell cultures offer a great opportunity to study biophysical properties of identified neurons in the central nervous system. Electrical properties of cultured neurons from various parts of the mammalian central nervous system (CNS) have been studied (1); however, there are several problems in such studies. The first problem is identification of a particular type of neuron in cell culture and the second is proof that the cells under investigation retain the properties of their physiological state. The third problem is to obtain stable electrical recordings from small neurons. Two recent technical advances overcome these three difficulties. Production of specific polyclonal and monoclonal antibodies allows the identification of several neurons in the mammalian CNS. With the patch (whole-cell) recording technique we can monitor electrical activities of cultured small cells and also control the intracellular ionic environment (2).The cerebellum is one of the best studied parts of the CNS (3, 4). Its neuronal circuit and development are well understood (3, 4), and several markers have already been found that specifically bind to Purkinje cells (5-7) and granule cells (8). Methods for culturing Purkinje cells (5) and granule cells (8-10) have also been established. In this study we applied the whole-cell patch-clamp technique to Purkinje cells in dissociated cell cultures and recorded various ionic currents. MATERIALS AND METHODSPrimary Culture. Purkinje cells were cultured as reported (5). In short, cerebella were dissected from rat fetuses on approximately embryonic day 20 and freed of meninges. The cerebella were incubated at 20°C for 4 min in 1% trypsin/0.05% DNase solution, which contained 137 mM NaCl, 5 mM KCl, 7 mM Na2PO4, and 25 mM Hepes (pH 7.2). After three washings with Ca-and Mg-free Hanks' balanced salt solution the tissue was dissociated by triturating with firepolished Pasteur pipets in Ca-free Hanks' balanced salt solution containing 0.05% DNase and 12 mM MgSO4. The cell suspension was centrifuged at 180 x g at 40C and the pelleted cells were resuspended at a concen...

show abstract

“…1). Two different monoclonal antibodies were used, 454A12 and OKT4 (14,24). The 454A12 monoclonal antibody, an IgG1, binds the human transferrin receptor, and OKT4, an IgG2, binds the human CD4 antigen on human T cells.…”

Section: Resultsmentioning

confidence: 99%

Diphtheria toxin mutant selectively kills cerebellar Purkinje neurons.

Riedel

Muraszko²,

Youle³

1990

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

CRM107 (crossreacting material 107), a double point mutant ofdiphtheria toxin that lacks receptor-binding activity, specifically kills cerebellar Purkinje cells in vivo. After injection into guinea pig cerebrospinal fluid, CRM107 (0.9 ,ug) and CRM107-monoclonal antibody conjugates (10 ,jg) kill up to 90% of the total Purkinje cell population with no detectable toxicity to other neurons. Animals exhibit ataxia, tremor, and abnormalities of posture and tone. Native diphtheria toxin, ricin, and ricin A chain do not cause ataxia and do not reduce the Purkinje cell population after intrathecal injection into guinea pigs at toxic or maximally tolerated doses. However, in rats, which will tolerate higher doses of diphtheria toxin than guinea pigs, Purkinje cells can be killed by both CRM107 and diphtheria toxin. A truncated mutant of diphtheria toxin, called CRM45, can also cause Purkinje cell killing but has additional toxicity not seen with CRM107. Animals treated with intrathecal CRM107 or CRM107 linked to antibodies may serve as models for Purkinje cell loss in a broad spectrum of human diseases and may be used to further study cerebellar physiology. Understanding the basis for the Purkinje cell sensitivity to CRM107 may illuminate other causes of Purkinje cell loss.

show abstract

Monoclonal antibodies against human T lymphocytes label Purkinje neurones of many species

Cited by 193 publications

References 18 publications

Expression of the CD6 T lymphocyte differentiation antigen in normal human brain☆

Expression of the CD6 T lymphocyte differentiation antigen in normal human brain☆

Voltage-gated and synaptic currents in rat Purkinje cells in dissociated cell cultures.

Diphtheria toxin mutant selectively kills cerebellar Purkinje neurons.

Contact Info

Product

Resources

About