Expression mapping of cytotoxic T-lymphocyte antigen-2α gene transcripts in mouse brain

Abstract

Cytotoxic T-lymphocyte antigen-2alpha (CTLA-2alpha), an inhibitor peptide homologous to the proregion of mouse cathepsin L, was originally discovered and expressed in mouse-activated T-cells and mast cells. Expressed recombinant CTLA-2alpha is shown to exhibit selective inhibition to cathepsin L-like cysteine proteinases. However, its in vivo targets in mammalian tissues are yet to be identified. We carried out in situ hybridization studies to examine the expression pattern of CTLA-2alpha mRNA and determine the specific cell types synthesizing CTLA-2alpha in the mouse brain. CTLA-2alpha mRNA was detected in various neuronal populations within the telencephalon in cerebral cortices, olfactory system, septum, basal ganglia, amygdala and highest levels were observed in the hippocampus. Within the diencephalon high density of positive cells was found in mediodorsal and lateral posterior thalamic nuclei and medial habenular nucleus (MHb). In the hypothalamus, high density of CTLA-2alpha mRNA labeling was seen in the suprachiasmatic nucleus (Sch), optic tract, arcuate nucleus, and median eminence. The fasciculus retroflexus and its termination in the mesencephalic interpeduncular nucleus were also densely labeled. Other mesencephalic expression sites were the superior colliculus, periaqueductal gray, paramedian raphe nucleus, and inferior colliculus. In the rhombencephalon, strong labeling was detected in the pontine, vestibular, and reticular nuclei. Intense expression was also noted within cerebellar cortex in Purkinje neurons and at a moderate level in granule cell layer, stellate, and basket cells. A possible function of this novel inhibitor peptide in relation to learning, memory, and diseases is discussed.

Changes of gene expression profiles in the cervical spinal cord by acupuncture in an MPTP-intoxicated mouse model: Microarray analysis

“…Cytotoxic T lymphocyte-associated protein 2 alpha (Ctla-2α) mRNA, a novel inhibitor of cysteine proteinase discovered in the activated T lymphocytes, is mainly enriched within mouse neuronal cells and its protein is known to be preferentially localized in the dendritic and axonal compartments in the various regions, including the basal ganglia, in the mouse brain (Luziga et al, 2007(Luziga et al, , 2008. Ctla-2α protein was strongly immunolocalized in the pyramidal tract in the medulla where there are a massive number of axons to transfer the neural information between the cerebral cortex and spinal cord, suggesting the involvement of Ctla-2α, which functions should be identified, in many neuronal biological processes (Luziga et al, 2008).…”

Induction of T Regulatory Cells by Cytotoxic T-Lymphocyte Antigen-2α on Corneal Endothelial Cells

“…In fact, CTLA-2 is most strongly expressed in the brain, the placenta, and the eyes. 6,8,9 These organs and tissues are considered immune-privileged sites. 10,11 Little is known of the tissue locations and physiological functions of CTLA-2␣ proteins in the eye.…”

Cytotoxic T lymphocyte antigen-2 alpha induces apoptosis of murine T-lymphoma cells and cardiac fibroblasts and is regulated by cAMP/PKA

“…CTLA-2α mRNA and protein are found not only in the T-lymphoma cells and cardiac fibroblasts that we assessed but also in neurons [25, 26], hematopoietic and germ-line stem cells and pregnant uteri [14, 15]. Recombinant CTLA-2α selectively inhibits cathepsin L-like cysteine proteinases, papain-like proteases of animal tissues [13].…”