We investigated the concentration of soluble CD4 molecules (sCD4) in serum, and the mechanism of sCD4 production from T lymphocytes, in patients with rheumatoid arthritis (RA). The concentration of sCD4 molecules was determined using a solid-phase enzyme-linked immunosorbent assay method. Using reverse transcription polymerase chain reaction (RT-PCR) techniques, we studied the presence of alternatively spliced mRNA encoding the transmembrane site of CD4, and the mRNA encoding a conservative region of the CD4 binding site of the human immunodeficiency virus (HIV), in the serum of RA patients. Levels of sCD4 found in RA patients were higher than in normal controls (199 U/ml compared with 8.4 U/ml, respectively), and correlated with additional medical parameters. The results of RT-PCR suggested that the higher sCD4 levels may be due to shedding from the cell membrane after protease digestion, not to alternative splicing or a reaction to viral binding to sCD4.
SwanLS: Significance of Lyt phenotypes: Lyt2 antibodies block activities of T cells that recognize Class 1 major histocompatibility complex antigens regardless of their function. Proc Natl Acad Sci U S A1981; 78: 7101–7105
2.
ParnesJR: Molecular biology and function of CD4 and CD8. Adv Immunol1989; 44: 265–311
3.
ReinherzELSchlossmanSF: The differentiation and function of human T lymphocytes. Cell1980; 19: 821–827
4.
WilliamsAFBarclayAN: The immunoglobulin superfamily domains for cell surface recognition. Annu Rev Immunol1988; 6: 381–405
5.
DalgleishAGBeverleyPCLClaphamPRCrawfordDHGreavesMFWeissRA: The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature1984; 312: 763–767
6.
VeilletteABookmanMAHorakEMBolenJB: The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell1988; 55: 301–308
7.
LittmanDR: The structure of the CD4 and CD8 genes. Annu Rev Immunol1987; 5: 561–584
8.
HusseyRCRichardsonNEKowalskiMBrownNRChangHCSilicianoRF: A soluble CD4 protein selectively inhibits HIV replication and syncytium formation. Nature1988; 331: 78–81
9.
ReddyMMVodianMHGriecoM: Elevated levels of CD4 antigen in sera of human immunodeficiency virus infected populations. J Clin Microbiol1990; 28: 1744–1746
10.
SalvaraniCBoiardiLMacchioniPMaldiniMCManciniRBeltrandiE: Serum soluble CD4 and CD8 levels in polymyalgia rheumatica. J Rheumatol1994; 21: 1865–1869
11.
TokanoYObaraTHashimotoHOkumuraKHiroseS: Soluble CD4, CD8 in patients with polymiositis/dermatomyositis. Clin Rheumatol1993; 12: 368–374
12.
D'CruzDDireskeneliHKhamashtaMHughesGV: Lymphocyte activation marker and von Willebrand Factor antigen in Wegener's granulomatosis: potential markers for disease activity. J Rheumatol1999; 26: 103–109
13.
UchioEMatsumotoTTanakaSIOhnoS: Soluble intercellular adhesion molecule-1 (ICAM-1), CD4, CD8 and interleukin-2 receptor in patients with Behçet's disease and Vogt-Koyanagi-Harada's disease. Clin Exp Rheumatol1999; 17: 179–184
14.
FurukawaSMatsubaraTTsujiKMotohashiTOkumuraKYabutaK: Serum soluble CD4 and CD8 levels in Kawasaki disease. Clin Exp Immunol1991; 86: 134–139
15.
YoneyamaANakaharaKHigashiharaMKurokawaK: Increased levels of soluble CD4 and CD8 in patients with infectious mononucleosis. Br J Haematol1995; 89: 47–54
16.
SawadaSSugaiSIijimaSTakeiMParedesEHayamaT: Increased soluble CD4 and decreased soluble CD8 molecules in patients with Sjögren's syndrome. Am J Med1992; 92: 134–140
17.
Kuryliszyn-MoskalA: Cytokines and soluble CD4 and CD8 molecules in rheumatoid arthritis: relationship to systemic vasculitis and microvascular capillaroscopic abnormalities. Clin Rheumatol1998; 17: 489–495
18.
GoronzyJJBartz-BazzanellaPHuWJendroMCWalser-KuntzDRWeyandCM: Dominant clonotypes in the repertoire of peripheral CD4+ T cells in rheumatoid arthritis. J Clin Invest1994; 94: 2068–2076
19.
SymonsJAMcCullochJFWoodNCDuffGW: Soluble CD4 in patients with rheumatoid arthritis and osteoarthritis. Clin Immunol Immunopathol1991; 60: 72–82
20.
DooleyMACushJJLipskyPEDawsonDVPisetskyDS: The effects of nonsteroidal antiinflammatory drug therapy in early rheumatoid arthritis on serum levels of soluble interleukin2 receptor, CD4 and CD8. J Rheumatol1993; 20: 1857–1862
21.
TakeiMMitamuraKFujiwaraSHorieTRyuJOsakaS: Detection of Epstein-Barr virus-encoded small RNA 1 and latent membrane protein 1 in synovial lining cells from rheumatoid arthritis patients. Int Immunol1997; 9: 739–743
22.
KitajimaIYamamotoKSatoKNakajimaYNakajimaTMaruyamaI: Detection of human T cell lymphotropic virus type I proviral DNA and its gene expression in synovial cells in chronic inflammatory arthropathy. J Clin Invest1991; 88: 1315–1322
23.
EguchiKOriguchiTTakashimaHIwataKKatamineSNagatakiS: High seroprevalence of anti-HTLV-I antibody in rheumatoid arthritis. Arthritis Rheum1996; 39: 463–466
24.
BlaschkeSSchwarzGMonekeDBinderLMullerGReuss-BorstM: Epstein-Barr virus infection in peripheral blood mononuclear cells, synovial fluid cells and synovial membranes of patients with rheumatoid arthritis. J Rheumatol2000; 27: 866–873
25.
TakedaTMizugakiYMatsubaraLImaiSKoikeTTakadaK: Lytic Epstein-Barr virus infection in the synovial tissue of patients with rheumatoid arthritis. Arthritis Rheum2000; 43: 1218–1225
26.
ArnattFCEdworthySBlockDAMcShaneDJFriesJFThe ARA Rheumatoid Arthritis Criteria Subcommittee: The 1987 revised ARA criteria for rheumatoid arthritis (RA). Arthritis Rheum1987; 30: S17
27.
AltmanRAschEBlochDBoleGBorensteinDBrandtK: Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Arthritis Rheum1986; 29: 1039–1049
28.
AltmanRAlarconGAppelrouthDBlochDBorensteinDBrandtK: The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum1991; 34: 505–514
29.
JuliusMHSimpsonEHerzenbergLA: A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol1973; 3: 645–649
30.
ChomczynskiPSacchiN: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem1987; 162: 156–159
31.
MaddonPJLittmanDRGodfreyMMaddonDEChessLAxelR: The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family. Cell1985: 42: 93–104
32.
KinoshitaTShimoyamaMTobibaiKItoMItoSIkedaS: Detection of mRNA for the taxl/rexl gene of human T-cell leukemia virus type 1 in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction. Proc Natl Acad Sci U S A1989; 86: 5620–5624
33.
LaskyLANakamuraGSmithDHFennieCShimasakiCPatzerE: Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell1987; 50: 975–985
34.
RobeyEAxelR: CD4: collaborator in immune recognition and HIV infection. Cell1990: 60: 697–700
35.
ArthosJDeenKCChaikinMAFornwaldJASatheGSattentauQJ: Identification of the residues in human CD4 critical for the binding of HIV. Cell1989; 57: 469–481
36.
ClaytonLKSiehMPiousDAReinherzEL: Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding. Nature1989; 339: 548–551
37.
FinbergRWDiamondDCMitchellDBRosensteinYSomanGNormanTC: Prevention of HIV-1 infection and preservation of CD4 function by the binding of CPFs to gp120. Science1990; 249: 287–291
38.
RatnerLHaseltineWPatarcaRLivakKJStarcichBJosephsSF: Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature1985; 313: 277–284
39.
NormentAMLonbergNLacyELittmanDR: Alternatively spliced mRNA encodes a secreted form of human CD8 alpha. Characterization of the human CD8 gene. J Immunol1989; 142: 3312–3319
40.
GiblinPLedbetterJAKavathasP: A secreted form of the human lymphocyte cell surface molecule CD8 arises from alternative splicing. Proc Natl Acad Sci U S A1989; 86: 998–1002
