WordNet

name or recite the numbers in ascending order; "The toddler could count to 100"
the total number counted; "a blood count"
the act of counting; reciting numbers in ascending order; "the counting continued for several hours" (同)counting, numeration, enumeration, reckoning, tally
a nobleman (in various countries) having rank equal to a British earl
have faith or confidence in; "you can count on me to help you any time"; "Look to your friends for support"; "You can bet on that!"; "Depend on your family in times of crisis" (同)bet, depend, look, calculate, reckon
have weight; have import, carry weight; "It does not matter much" (同)matter, weigh
put into a group; "The academy counts several Nobel Prize winners among its members" (同)number
determine the number or amount of; "Can you count the books on your shelf?"; "Count your change" (同)number, enumerate, numerate
have a certain value or carry a certain weight; "each answer counts as three points"
include as if by counting; "I can count my colleagues in the opposition"
the 3rd letter of the Roman alphabet (同)c
(music) the keynote of the scale of C major
a general-purpose programing language closely associated with the UNIX operating system

PrepTutorEJDIC

(一つ一つ順に)〈数〉'を'『数える』,〈物〉'を'数え上げる《+『up』+『名,』+『名』+『up』》 / …'を'『勘定に入れる』,含める(include) / …'を'『思う』,みなす(consider) / 数を数える,計算する《+『up』》 / 数にはいる,数に含まれる / 価値がある,重大である / 〈C〉〈U〉『数えること』,『計算』 / 〈U〉総数,総計 / 〈U〉(起訴状の)訴因 / 《the~》(ボクシングで)カウント(選手がノックダウンされたときレフリーが1から10まで数えること) / 〈C〉(野救で打者の)ボールカウント / 〈U〉《話》考慮,注目(account)
(英国以外の)伯爵
carbonの化学記号
certificate of deposit / (また『C.D.』)Civil Defense民間防衛

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/02 02:23:19」(JST)

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Image of CD4 co-receptor binding to MHC (Major Histocompatibility Complex) non-polymorphic region.

In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 (after the OKT4 monoclonal antibody that reacted with it) before being named CD4 in 1984.^[2] In humans, the CD4 protein is encoded by the CD4 gene.^[3]^[4]

CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells. They are called helper cells because one of their main roles is to send signals to other types of immune cells, including CD8 killer cells, which then destroy the infectious particle. If CD4 cells become depleted, for example in untreated HIV infection, or following immune suppression prior to a transplant, the body is left vulnerable to a wide range of infections that it would otherwise have been able to fight.

Structure

Schematic representation of CD4 receptor.

Like many cell surface receptors/markers, CD4 is a member of the immunoglobulin superfamily.

It has four immunoglobulin domains (D₁ to D₄) that are exposed on the extracellular surface of the cell:

D₁ and D₃ resemble immunoglobulin variable (IgV) domains.
D₂ and D₄ resemble immunoglobulin constant (IgC) domains.

CD4 uses its D₁ domain to interact with the β₂-domain of MHC class II molecules. T cells expressing CD4 molecules (and not CD8) on their surface, therefore, are specific for antigens presented by MHC II and not by MHC class I (they are MHC class II-restricted). MHC class I contains Beta-2 microglobulin.

The short cytoplasmic/intracellular tail (C) of CD4 contains a special sequence of amino acids that allow it to interact with the lck molecule.

Function

CD4 is a co-receptor that assists the T cell receptor (TCR) in communicating with an antigen-presenting cell. Using its intracellular domain, CD4 amplifies the signal generated by the TCR by recruiting an enzyme, the tyrosine kinase Lck, which is essential for activating many molecular components of the signaling cascade of an activated T cell. Various types of T helper cells are thereby produced. CD4 also interacts directly with MHC class II molecules on the surface of the antigen-presenting cell using its extracellular domain. The extracellular domain adopts an immunoglobulin-like beta-sandwich with seven strands in 2 beta sheets, in a Greek key topology.^[5]

Other Interactions

CD4 has also been shown to interact with SPG21,^[6] Lck^[7]^[8]^[9]^[10]^[11] and Protein unc-119 homolog.^[12]

Disease

HIV infection

HIV-1 uses CD4 to gain entry into host T-cells and achieves this through its viral envelope protein known as gp120.^[13] The binding to CD4 creates a shift in the conformation of gp120 allowing HIV-1 to bind to a co-receptor expressed on the host cell. These co-receptors are chemokine receptors CCR5 or CXCR4. Following a structural change in another viral protein (gp41), HIV inserts a fusion peptide into the host cell that allows the outer membrane of the virus to fuse with the cell membrane.

HIV pathology

HIV infection leads to a progressive reduction in the number of T cells expressing CD4. Medical professionals refer to the CD4 count to decide when to begin treatment during HIV infection. Normal blood values are usually expressed as the number of cells per microliter (or cubic millimeter, mm³) of blood, with normal values for CD4 cells being 500-1200 cells/mm³.^[14] A CD4 count measures the number of T cells expressing CD4. While CD4 counts are not a direct HIV test--e.g. they do not check the presence of viral DNA, or specific antibodies against HIV--they are used to assess the immune system of a patient. Patients often undergo treatments when the CD4 counts reach a level of 350 cells per microliter in Europe but usually around 500cpm in the US; people with less than 200 cells per microliter are at high risk of contracting AIDS defined illnesses. The newest National Institute of Health guidelines recommend treatment of any HIV-positive individuals, regardless of CD4 count^[15] Medical professionals also refer to CD4 tests to determine efficacy of treatment.

Reference ranges for blood tests of white blood cells, comparing CD4+ cell amount (shown in green-yellow) with other cells.

Other diseases

CD4 continues to be expressed in most neoplasms derived from T helper cells. It is therefore possible to use CD4 immunohistochemistry on tissue biopsy samples to identify most forms of peripheral T cell lymphoma and related malignant conditions.^[16] The antigen has also been associated with a number of autoimmune diseases such as vitiligo and type I diabetes mellitus.^[17]

References

^ PDB 1cdh; Ryu SE, Truneh A, Sweet RW, Hendrickson WA (January 1994). "Structures of an HIV and MHC binding fragment from human CD4 as refined in two crystal lattices". Structure 2 (1): 59–74. doi:10.1016/s0969-2126(00)00008-3. PMID 8075984.
^ Bernard A, Boumsell L, Hill C (1984). "Joint Report of the First International Workshop on Human Leucocyte Differentiation Antigens by the Investigators of the Participating Laboratories". In Bernard A, Boumsell L, Dausset J, Milstein C, Schlossman SF. Leucocyte typing: human leucocyte differentiation antigens detected by monoclonal antibodies: specification, classification, nomenclature. Berlin: Springer. pp. pages 45–48. doi:10.1007/978-3-642-68857-7_3. ISBN 0-387-12056-4. Report on the first international references workshop sponsored by INSERM, WHO and IUIS
^ Isobe M, Huebner K, Maddon PJ, Littman DR, Axel R, Croce CM (June 1986). "The gene encoding the T-cell surface protein T4 is located on human chromosome 12". Proc. Natl. Acad. Sci. U.S.A. 83 (12): 4399–402. doi:10.1073/pnas.83.12.4399. PMC 323740. PMID 3086883.
^ Ansari-Lari MA, Muzny DM, Lu J, Lu F, Lilley CE, Spanos S et al. (April 1996). "A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13". Genome Res. 6 (4): 314–26. doi:10.1101/gr.6.4.314. PMID 8723724.
^ Brady RL, Dodson EJ, Dodson GG, Lange G, Davis SJ, Williams AF et al. (May 1993). "Crystal structure of domains 3 and 4 of rat CD4: relation to the NH2-terminal domains". Science 260 (5110): 979–83. doi:10.1126/science.8493535. PMID 8493535.
^ Zeitlmann L, Sirim P, Kremmer E, Kolanus W (Mar 2001). "Cloning of ACP33 as a novel intracellular ligand of CD4". J. Biol. Chem. 276 (12): 9123–32. doi:10.1074/jbc.M009270200. PMID 11113139.
^ Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF (September 2010). "Pillars article: the CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. 1988". J. Immunol. 185 (5): 2645–9. PMID 20724730.
^ Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF (July 1988). "The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes". Proc. Natl. Acad. Sci. U.S.A. 85 (14): 5190–4. doi:10.1073/pnas.85.14.5190. PMC 281714. PMID 2455897.
^ Barber EK, Dasgupta JD, Schlossman SF, Trevillyan JM, Rudd CE (May 1989). "The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex". Proc. Natl. Acad. Sci. U.S.A. 86 (9): 3277–81. doi:10.1073/pnas.86.9.3277. PMC 287114. PMID 2470098.
^ Hawash IY, Hu XE, Adal A, Cassady JM, Geahlen RL, Harrison ML (April 2002). "The oxygen-substituted palmitic acid analogue, 13-oxypalmitic acid, inhibits Lck localization to lipid rafts and T cell signaling". Biochim. Biophys. Acta 1589 (2): 140–50. doi:10.1016/S0167-4889(02)00165-9. PMID 12007789.
^ Foti M, Phelouzat MA, Holm A, Rasmusson BJ, Carpentier JL (February 2002). "p56Lck anchors CD4 to distinct microdomains on microvilli". Proc. Natl. Acad. Sci. U.S.A. 99 (4): 2008–13. doi:10.1073/pnas.042689099. PMC 122310. PMID 11854499.
^ Gorska MM, Stafford SJ, Cen O, Sur S, Alam R (February 2004). "Unc119, a Novel Activator of Lck/Fyn, Is Essential for T Cell Activation". J. Exp. Med. 199 (3): 369–79. doi:10.1084/jem.20030589. PMC 2211793. PMID 14757743.
^ Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA (June 1998). "Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody". Nature 393 (6686): 648–59. doi:10.1038/31405. PMID 9641677.
^ Bofill M, Janossy G, Lee CA, MacDonald-Burns D, Phillips AN, Sabin C et al. (May 1992). "Laboratory control values for CD4 and CD8 T lymphocytes. Implications for HIV-1 diagnosis". Clin. Exp. Immunol. 88 (2): 243–52. PMC 1554313. PMID 1349272.
^ "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents" (PDF). AIDSinfo. U.S. Department of Health & Human Services. 2013-02-13.
^ Kumarasen Cooper; Anthony S-Y. Leong (2003). Manual of diagnostic antibodies for immunohistology. London: Greenwich Medical Media. p. 65. ISBN 1-84110-100-1.
^ Zamani M, Tabatabaiefar MA, Mosayyebi S, Mashaghi A, Mansouri P (July 2010). "Possible association of the CD4 gene polymorphism with vitiligo in an Iranian population". Clin. Exp. Dermatol. 35 (5): 521–4. doi:10.1111/j.1365-2230.2009.03667.x. PMID 19843086.

External links

CD1 Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
Mouse CD Antigen Chart
Human CD Antigen Chart
*Human Immunodeficiency Virus Glycoprotein 120

This article incorporates text from the public domain Pfam and InterPro IPR015274

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. HIV感染患者におけるCD4細胞数の測定手技および解釈 techniques and interpretation of measurement of the cd4 cell count in hiv infected patients
2. HIV感染患者における日和見感染の予防の概要 overview of prevention of opportunistic infections in hiv infected patients
3. 肺症状を伴うHIV感染患者に対するアプローチ approach to the hiv infected patient with pulmonary symptoms
4. 特発性CD4陽性リンパ球減少症 idiopathic cd4 lymphocytopenia
5. HIV感染患者における抗レトロウイルス療法の開始時期 when to initiate antiretroviral therapy in hiv infected patients

English Journal

Electrochemical magneto-actuated biosensor for CD4 count in AIDS diagnosis and monitoring.

Carinelli S1, Xufré Ballesteros C2, Martí M2, Alegret S1, Pividori MI3.
Biosensors & bioelectronics.Biosens Bioelectron.2015 Dec 15;74:974-80. doi: 10.1016/j.bios.2015.07.053. Epub 2015 Jul 26.
The counting of CD4(+) T lymphocytes is a clinical parameter used for AIDS diagnosis and follow-up. As this disease is particularly prevalent in developing countries, simple and affordable CD4 cell counting methods are urgently needed in resource-limited settings. This paper describes an electrochem
PMID 26264263

Clinical and laboratory characteristics of ocular syphilis: a new face in the era of HIV co-infection.

Lee SY1, Cheng V, Rodger D, Rao N.
Journal of ophthalmic inflammation and infection.J Ophthalmic Inflamm Infect.2015 Dec;5(1):56. doi: 10.1186/s12348-015-0056-x. Epub 2015 Aug 22.
BACKGROUND: Ocular syphilis is reemerging as an important cause of uveitis in the new era of common co-infection with HIV. This study will reveal the clinical and laboratory characteristics in the group of individuals co-infected with ocular syphilis and HIV compared with HIV-negative individuals. I
PMID 26297110

Design and structure of the Estonian HIV Cohort Study (E-HIV).

Soodla P1, Rajasaar H, Avi R, Zilmer K, Kink K, Novikova L, Huik K, Maimets M, Lutsar I.
Infectious diseases (London, England).Infect Dis (Lond).2015 Nov;47(11):772-9. doi: 10.3109/23744235.2015.1061203. Epub 2015 Jul 8.
BACKGROUND: Estonia is experiencing the new Eastern Europe human immunodeficiency virus (HIV) epidemic, with the highest incidence of new infections in the EU. We describe demographic changes, HIV-related laboratory parameters and co-infections during the concentrated HIV epidemic using the Estonian
PMID 26153824

Japanese Journal

日本人男性HIV陽性者における,CD4<500/mm³群とCD4≧500/mm³群での栄養状態の差異

日本エイズ学会誌 = The journal of AIDS research 18(1), 29-39, 2016
NAID 40020754758

自己免疫性小脳失調症の可能性が示唆されたHIV感染症の1例

臨床神経学 56(4), 255-259, 2016
NAID 130005149741

自己免疫性小脳失調症の可能性が示唆されたHIV感染症の1例

臨床神経学 advpub(0), 2016
NAID 130005139516

「CD4+ count」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

CD4, Cluster of differentiation 4, extracellular
	structure of t-cell surface glycoprotein cd4, monoclinic crystal form
Identifiers
Symbol	CD4-extrcel
Pfam	PF09191
InterPro	IPR015274
SCOP	1cid
SUPERFAMILY	1cid
OPM superfamily	230
OPM protein	2klu
CDD	cd07695
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

CD4 molecule
	; Crystallographic structure of the V-set and C2 domains of human CD4.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1CDH, 1CDI, 1CDJ, 1CDU, 1CDY, 1G9M, 1G9N, 1GC1, 1JL4, 1OPN, 1OPT, 1OPW, 1Q68, 1RZJ, 1RZK, 1WBR, 1WIO, 1WIP, 1WIQ, 2B4C, 2JKR, 2JKT, 2KLU, 2NXY, 2NXZ, 2NY0, 2NY1, 2NY2, 2NY3, 2NY4, 2NY5, 2NY6, 2QAD, 3B71, 3CD4, 3JWD, 3JWO, 3LQA, 3O2D, 3S4S, 3S5L, 3T0E, 4H8W, 4JM2, 4P9H
Identifiers
Symbols	CD4 ; CD4mut
External IDs	OMIM: 186940 MGI: 88335 HomoloGene: 513 ChEMBL: 2754 GeneCards: CD4 Gene
Gene ontology
Molecular function	• glycoprotein binding; • receptor activity; • transmembrane signaling receptor activity; • extracellular matrix structural constituent; • protein binding; • zinc ion binding; • coreceptor activity; • enzyme binding; • protein kinase binding; • MHC class II protein binding; • protein homodimerization activity;
Cellular component	• early endosome; • endoplasmic reticulum lumen; • endoplasmic reticulum membrane; • plasma membrane; • external side of plasma membrane; • integral component of membrane; • T cell receptor complex; • membrane raft;
Biological process	• cytokine production; • induction by virus of host cell-cell fusion; • immune response; • cell adhesion; • signal transduction; • cell surface receptor signaling pathway; • enzyme linked receptor protein signaling pathway; • transmembrane receptor protein tyrosine kinase signaling pathway; • viral process; • T cell differentiation; • entry into host cell; • T cell costimulation; • maintenance of protein location in cell; • T cell selection; • positive regulation of interleukin-2 biosynthetic process; • innate immune response; • protein palmitoleylation; • positive regulation of protein kinase activity; • regulation of defense response to virus by virus; • positive regulation of peptidyl-tyrosine phosphorylation; • defense response to Gram-negative bacterium; • positive regulation of calcium-mediated signaling; • T cell receptor signaling pathway; • regulation of T cell activation;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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