Disease relevance of CD69

• We investigated whether autoantibodies to CD69, one of the earliest markers of lymphocyte activation, exist in the sera of patients with systemic autoimmune disease [1].
• RESULTS: The fraction of tonsillar CD8 T cells expressing CD69, CD38, or HLA-DR in the patients with suppressed virus replication declined to levels comparable with that in controls by 48 weeks and showed a strong positive correlation with tonsillar infectious provirus and plasma viremia [2].
• Increased CD69 and human leukocyte antigen-DR expression on T lymphocytes in insulin-dependent diabetes mellitus of long standing [3].
• The results indicated that following stimulation with IPP, gamma delta T cells express CD25 and CD69 antigens, but fail to proliferate unless growth factors are provided exogenously or endogenously through activation of CD4 T cells by additional stimuli such as tetanus toxoid, alloantigen, or superantigens [4].
• In addition, CD69 is a useful immunohistochemical marker for specific T cell lymphomas in frozen and paraffin-embedded tissue [5].

Psychiatry related information on CD69

• Among SEB-activated lymphocytes, CD45RO+CD45RA- lymphocytes showed enhanced locomotor responses, but a relation was not found between locomotor activity and the presence of cell surface CD69 [6].
• DESIGN AND METHODS: Whole blood from patients with HAD, HIV seronegative subjects, and HIV seropositive subjects with no dementia (HIV-ND) was analyzed for CD14/CD69 cells using flow cytometry [7].

High impact information on CD69

• After transduction into T cells, the Hph-1-ctCTLA-4 fusion protein inhibited the production of interleukin (IL)-2, and downregulated CD69 and CD25 [8].
• Antibodies against CD69, LFA-1 or ICAM-1 significantly inhibited the ability of T cells to activate macrophages by cell contact [9].
• Raft targeting of activated SHP-1 in Jurkat-derived transfectants completely inhibited the expression of CD69 and transcriptional factors after TCR cross-linking [10].
• Here, we report that PKCtheta function was selectively required in a Vav signaling pathway that mediates the TCR/CD28-induced activation of JNK and the IL-2 gene and the upregulation of CD69 expression [11].
• MHC dimers, trimers, and tetramers stimulated T cells, as measured by upregulation of the activation markers CD69 and CD25, and by internalization of activated T cell receptor subunits [12].

Chemical compound and disease context of CD69

• Ischemia and further reperfusion resulted in significant rise in nitrite and nitrate levels (p < 0.001), interleukin-6 (p < 0.01), CD62L (p < 0.001), CD69 (p < 0.05), protein kinase C (p < 0.001) and intracellular calcium (p < 0.001) [13].
• Fresh NK cells were activated, as indicated by the induced expression of the CD69 antigen, and their cytolytic activity was strongly augmented by contact with lipopolysaccharide (LPS)-treated mature DC, or with immature DC in the presence of the maturation stimuli LPS, Mycobacterium tuberculosis or interferon (IFN)-alpha [14].
• Methimazole therapy in Graves' disease influences the abnormal expression of CD69 (early activation antigen) on T cells [15].
• CD69 expression on peripheral CD4+ T cells parallels disease activity and is reduced by mycophenolate mofetil therapy in uveitis [16].
• The CD3+ PBL from HIV+ or HIV- donors did not show increased CD69 expression after culture with soluble or cross-linked recombinant envelope glycoprotein, gp120 [17].

Biological context of CD69

• The isolated cDNA exhibited a single open reading frame of 597 bp coding for CD69, and predicted a 199-amino acid protein of type II membrane topology, with extracellular (COOH-terminal), transmembrane, and intracellular domains [18].
• ORF5 expression resulted in the marked augmentation of TCR signal transduction activity, evidenced by increased cellular tyrosine phosphorylation, intracellular calcium mobilization, CD69 surface expression, interleukin-2 production, and activation of the NF-AT, NF-kappa B, and AP-1 transcription factors [19].
• TCR stimulation of JCaM1/Fyn cells induced the expression of the CD69 activation marker and inhibited cell growth, but NFAT activation and the production of interleukin-2 were markedly reduced [20].
• When T cells were stimulated with Bead-Leu4 in microgravity culture, they were able to partially express CD69, a receptor that is constitutively stored in intracellular pools and can be expressed in the absence of new gene expression [21].
• Homology searches revealed sequence similarity with members of a supergene family of type II integral membrane proteins with a C-type lectin domain, indicating that CD69 is involved in signal transduction [22].

Anatomical context of CD69

• The activation of T lymphocytes, both in vivo and in vitro, induces the expression of CD69 [18].
• The CD69 clone hybridized to a 1.7-kb mRNA species, which was rapidly induced and degraded after lymphocyte stimulation, consistent with the presence of rapid degradation signals at the 3' untranslated region [18].
• Anti-p75 IL-2R mAb substantially inhibits the early events associated with NK cell activation by IL-2, including inhibition of cytotoxic activity and induction of the CD69 early activation antigen [23].
• These eosinophils have an increased viability and CD69 expression 18 h after segmental allergen provocation (SAP) which is not present in peripheral blood [24].
• Transient expression of the polypeptide encoded by CD69 cDNA in COS-7 cells demonstrated that it presented properties comparable to native CD69 protein [18].

Associations of CD69 with chemical compounds

• The physiologic relevance of these signaling events is further supported by the finding of PLCgamma1 tyrosine phosphorylation, Erk activation, and CD69 upregulation in P116 cells on stimulation with superantigen and antigen-presenting cells [25].
• Ver and Tmx did not interfere with T-cell activation as determined by CD25 and CD69 expression [26].
• In the attempt to elucidate the function of CD69 we investigated the ability of the CD69 glycoprotein to transmit an activation signal [27].
• CD40-L expression was not inducible in 28 of 30 specimens of newborn cord-blood T cells following incubation with PMA and ionomycin, whereas activation markers such as CD69 were inducible [28].
• Phosphorylation of the LFA-1 Integrin beta2-Chain on Thr-758 Leads to Adhesion, Rac-1/Cdc42 Activation, and Stimulation of CD69 Expression in Human T Cells [29].

Physical interactions of CD69

• Analysis of enhancer deletion mutants revealed that proximal AP-1, OCT-1/octamer-associated protein and nuclear factor of activated T cells (NFAT) binding regions were all necessary to allow CD69-mediated enhancement of CAT activity [30].

Enzymatic interactions of CD69

• CD69 is a phosphorylated disulfide-linked homodimer that appears on the surface of human T, B cells and thymocytes in the early steps of activation; its molecular mass is 28 to 34 kDa under reducing conditions [31].

Regulatory relationships of CD69

• When the two mAbs were used in combination, anti-CD28 potently synergized with anti-CD3 in inducing the expression of CD69 activation marker and stimulating the proliferation of CD4+ T cells [32].
• Finally, we found that the IL-2-induced expression of CD69 was inhibited by activation of cAMP-dependent protein kinase and by inhibition of the Src-family of the tyrosine protein kinase, but not by inhibition of protein kinase C or by activation of the CD45 associated tyrosine phosphatase [33].
• Exogenous IL-15 resulted in further enhancement of anti-CD3-induced CD69 expression to a greater extent than that achieved with IL-2 [34].
• In contrast, the phorbol esters, PdBu or PMA had little effect on CXCR6 expression (23% reduction) but induced CD69 expression and caused a profound down-regulation (92%) of CCR5 expression [35].
• CONCLUSION: The activation antigen CD69 is significantly expressed on PB and SF neutrophils from RA patients [36].

Other interactions of CD69

• Although the two compounds had distinctive effects on CD69 induction, they both suppressed T cell proliferation induced by anti-CD3 mAb, in a manner reversible by exogenous IL-2, suggesting that PD98059, like FK506, affects the production of, rather than the responsiveness to growth-promoting cytokines [37].
• This autoantibody may modulate the function of CD69- and LRP2-expressing cells [1].
• Cross-linking of CD53 with the use of the mAb MEM-53 and a polyclonal sheep anti-mouse Ig promoted activation of resting B cells into the G1 phase of the cell cycle as judged by increased expression of the early activation Ag CD69, increases in cellular volume, RNA synthesis, and c-myc protein levels, and enhanced binding of 7-aminoactinomycin D [38].
• METHODS: The percentage expression and mean fluorescence intensity of CR2 (and three additional markers: CD19, CD69, and a standard antigen designation: HLA-DR) was measured on CD20+ B-cells using a two-color flow cytometric assay [39].
• OBJECTIVE: It has been well established that CD69, CD44, and CD54 represent "activation markers" for cytokine-mediated eosinophil activation [40].

Analytical, diagnostic and therapeutic context of CD69

• Molecular cloning, expression, and chromosomal localization of the human earliest lymphocyte activation antigen AIM/CD69, a new member of the C-type animal lectin superfamily of signal-transmitting receptors [18].
• Sequence analysis of the 5'-flanking region of the CD69 gene revealed the presence of a potential TATA element 30 base pairs upstream of the major transcription initiation site and several putative binding sequences for inducible transcription factors (NF-kappa B, Egr-1, AP-1), which might mediate the inducible expression of this gene [41].
• Furthermore, bronchoalveolar lavage fluid basophils showed higher levels of CD69 expression than did blood basophils from the same donors [40].
• Expression of CD69 and HLA-DR on lymphocytes and monocytes, as well as lipopolysaccharide (LPS) binding, were measured by flow cytometry [42].
• In contrast, patients with renal allograft rejection showed significantly elevated percentages of CD69+ cells in the CD3+ (P<0.01) and CD8+ subsets (P<0.01) [43].

References