Regional distribution and partial molecular characterization of CD4-related mRNA in human brain and peripheral tissues

doi:10.1016/0169-328X(91)90052-Y

Molecular Brain Research

Volume 10, Issue 1, April 1991, Pages 23-31

https://doi.org/10.1016/0169-328X(91)90052-Y Get rights and content

Abstract

We purified human poly(A)⁺ RNA from 11 individuals to assess the regional distribution of CD4 and CD4-related mRNA transcripts in human brain and in peripheral tissues by Northern blot hybridization. A 3.0 kb CD4 mRNA transcript was expressed in all brain areas and several peripheral tissues examined. A second CD4-related 1.8 kb mRNA species showed an uneven distribution in the brain with cortical regions possessing highest levels and basal ganglia, thalamus, cerebellum and spinal cord containing relatively lower amounts. Messenger RNA transcripts for CD8, a T cell specific marker, were not detectable in human brain by Northern analysis, yet were as abundant as CD4 in spleen. The expression of the 1.8 kb mRNA was tissue specific as it was not observed in peripheral tissues such as spleen, adrenal, colon, or lung, nor was it found in the choroid plexus, dorsal root ganglion and human neuronal (SY5Y) or astroglial (N132N1) cell lines. Blot hydridization and S1 nuclease protection analysis of poly(A)⁺ RNA with selective probes derived from CD4 indicated that the 1.8 kb mRNA transcript is truncated, lacking the extracellular protein coding region of CD4, and may in fact be a unique transcript from the CD4 gene locus rather than an alternatively spliced or processed CD4 mRNA.

References (43)

P.J. Maddon et al.
The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain
Cell
(1986)
H. Okayama et al.
High-efficiency cloning of full-length cDNA; construction and screening of cDNA expression libraries for mammalian cells
Methods. Enzymol.
(1987)
C.D. Pauza
HIV persistence in monocytes leads to pathogenesis and AIDS
Cell. Immunol.
(1988)
V.H. Perry et al.
Macrophages and microglia in the nervous system
TINS
(1988)
S.Z. Salahuddin et al.
Human T lymphotropic virus type III infection of human alveolar macrophages
Blood
(1986)
Q.J. Sattentau et al.
The CD4 antigen: physiological ligand and HIV receptor
Cell
(1988)
C. Cheng-Mayer et al.
Human immunodeficiency virus can productively infect cultured human glial cells
J.M. Chirgwin et al.
Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease
Biochemistry
(1979)
P.R. Clapham et al.
Soluble CD4 blocks the infectivity of diverse strains of HIV and SIV for T cells and monocytes but not for brain and muscle cells
Nature
(1989)
P.R. Crocker et al.
Species heterogeneity in macrophage expression of the CD4 antigen
J. Exp. Med.
(1987)

R. Collman et al.

Macrophage-tropic strains of human immunodeficiency virus type I utilize the CD4 receptor

J. Virol.

(1990)

A.G. Dalgleish et al.

The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus

Nature

(1984)

S.M. De la Monte et al.

Subacute encephalomyelitis of AIDS and its relation to HTLV-III infection

Neurology

(1987)

C. Doyle et al.

Interaction between CD4 and class II MHC molecules mediates cell adhesion

Nature

(1987)

D.J. Eilbott et al.

Human immunodeficiency virus type I in spinal cords of acquired immunodeficiency syndrome patients with myelopathy: expression and replication in macrophages

I. Funke et al.

The cellular receptor (CD4) of the human immunodeficiency virus is expressed on neurons and glial cells in human brain

J. Exp. Med.

(1987)

D.H. Gabuzda et al.

Immunohistochemical identification of HTLV-III antigens in brains of patients with AIDS

Ann. Neurol.

(1986)

D.H. Gabuzda et al.

Neurologic manifestations of infection with human immunodeficiency virus

Ann. Int. Med.

(1987)

S. Gartner et al.

The role of mononuclear phagocytes in HTLV-III/LAV infection

Science

(1986)

M.S. Gottlieb et al.

Pneumocystis carinii pneumonia and mucosal candidiosis in previously healthy homosexual men

N. Engl. J. Med.

(1981)

S. Gordon

The biology of the macrophage

J. Cell Sci.

(1986)

Cited by (9)

The differential role of spinal MHC class II and cellular adhesion molecules in peripheral inflammatory versus neuropathic pain in rodents
2002, Journal of Neuroimmunology
The present study was designed to determine the role of central expression of immunoregulatory molecules in the development and maintenance of allodynia following a peripheral inflammatory insult or nerve transection. Differential spinal expression of major histocompatibility complex (MHC) class II, platelet-endothelial cellular adhesion molecule (PECAM), intercellular adhesion molecule (ICAM) and CD4 was observed in the two injury models. Intraplantar zymosan produced transient allodynia and only PECAM and ICAM immunoreactivity. In contrast, persistent mechanical allodynia and enhanced spinal PECAM, ICAM, MHC class II and CD4 immunoreactivity was observed following peripheral nerve transection. MHC class II knockout mice exhibited attenuated allodynia following spinal nerve transection as compared to wild-type control mice. These findings suggest that central neuroimmune activation may contribute to the maintenance of neuropathic pain following peripheral L5 spinal nerve transection but not following a peripheral inflammatory insult.
Differential expression of inflammatory mediators in rat microglia cultured from different brain regions
1999, Molecular Brain Research
Microglial cells show a rather uniform distribution of cell numbers throughout the brain with only minor prevalences in some brain regions. Their in situ morphologies, however, may vary markedly from elongated forms observed in apposition with neuronal fibers to spherical cell bodies with sometimes extremely elaborated branching. This heterogeneity gave rise to the hypothesis that these cells are differentially conditioned by their microenvironment and, therefore, also display specific patterns of differential gene expression. In this study, microglia were isolated from 2–4 week-old mixed CNS cultures that had been prepared from neonatal rat diencephalon, tegmentum, hippocampus, cerebellum and cerebral cortex, and were investigated 24 h later. Messenger RNA levels of proteins involved in crucial immune functions of this cell type (TNF-α, CD4, Fcγ receptor II, and IL-3 receptor β-subunit) have been determined by semi-quantitative RT-PCR. The results clearly show, that three of these mRNAs (TNF-α, CD4, Fcγ receptor II) are differentially expressed in microglia with hippocampal microglia displaying the highest levels of these mRNAs. The data strongly support the notion that the status of microglial gene expression depends on their localization in brain and on specific interactions with other neural cell types. Consequently, it is hypothesized that their responsiveness to signals arising in injury or disease may vary from one brain region to another.
Embryonic expression of the mRNA for the rat homologue of the fusin/CXCR-4 HIV-1 co-receptor
1997, Journal of Neuroimmunology
We have previously cloned a human receptor recently shown to be a cofactor for entry of T-tropic HIV-1 strains into CD4+ cells, now named fusin. Stromal derived factor-1 (SDF-1) is an endogenous ligand for fusin, also called CXCR-4. Here we show the distribution of fusin/CXCR-4 mRNA during ontogeny in the rat. The onset of mRNA expression is around embryonic day 9 and the mRNA expression is high in the thymus as well as proliferative areas of the brain during development. Our results suggest: (1) that fusin/CXCR-4 might have a dual role in both brain development and the immune system; (2) that SDF-1 has a role in brain development or that additional physiological ligands exist for this receptor; (3) co-expression of CD4 and fusin/CXCR-4 may make fetuses susceptible to HIV infection during development.
HIV interactions with cells of the nervous system
1995, Current Opinion in Neurobiology
HIV can invade the CNS, where it replicates principally in macrophages. Yet, neurological disease is more often correlated with levels of neurotoxins or tumor necrosis factor α than with viral replication or specific viral determinants in brain. In experimental systems, HIV glycoprotein affects functions of uninfected microglia and astrocytes to eventually cause neuronal death. While the cellular basis of cognitive and neurological dysfunction are unravelled in the simian immunodeficiency virus model, the molecular mechanisms of HIV neurotoxicity are being studied in newly developed mouse models.
Isolated human astrocytes are not susceptible to infection by M- and T- tropic HIV-1 strains despite functional expression of the chemokine receptors CCR5 and CXR4
2001, GLIA
Expression of a novel form of the p56lck protooncogene in rat cerebellar granular neurons
1996, Journal of Neurochemistry

View all citing articles on Scopus

View full text

Research reportRegional distribution and partial molecular characterization of CD4-related mRNA in human brain and peripheral tissues

Abstract

Cell

Methods. Enzymol.

Cell. Immunol.

TINS

Blood

Cell

Human immunodeficiency virus can productively infect cultured human glial cells

Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

Biochemistry

Soluble CD4 blocks the infectivity of diverse strains of HIV and SIV for T cells and monocytes but not for brain and muscle cells

Nature

Species heterogeneity in macrophage expression of the CD4 antigen

J. Exp. Med.

Macrophage-tropic strains of human immunodeficiency virus type I utilize the CD4 receptor

J. Virol.

The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus

Nature

Subacute encephalomyelitis of AIDS and its relation to HTLV-III infection

Neurology

Interaction between CD4 and class II MHC molecules mediates cell adhesion

Nature

Human immunodeficiency virus type I in spinal cords of acquired immunodeficiency syndrome patients with myelopathy: expression and replication in macrophages

The cellular receptor (CD4) of the human immunodeficiency virus is expressed on neurons and glial cells in human brain

J. Exp. Med.

Immunohistochemical identification of HTLV-III antigens in brains of patients with AIDS

Ann. Neurol.

Neurologic manifestations of infection with human immunodeficiency virus

Ann. Int. Med.

The role of mononuclear phagocytes in HTLV-III/LAV infection

Science

Pneumocystis carinii pneumonia and mucosal candidiosis in previously healthy homosexual men

N. Engl. J. Med.

The biology of the macrophage

J. Cell Sci.

Research report
Regional distribution and partial molecular characterization of CD4-related mRNA in human brain and peripheral tissues