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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The existence of distinct subsets of memory CD8 T cells with different characteristics is now well established. In this work, we describe two subsets of mouse CD8 T cells with memory characteristics that coexist in primed thymectomized TCR-transgenic F5 mice and that share some properties with the human central and effector memory cells. The first subset corresponds to CD8 T cells generated following nucleoprotein 68 peptide priming which are CD44(int)CD122(-)nucleoprotein 68/H-2D(b) tetramer(+) and express high levels of CCR7 mRNA. In contrast, CD8 T cells in the second subset are CD44(high)CD122(+), are heterogeneous in terms of Ag specificity, and express low levels of CCR7 mRNA. We have studied the functional characteristics and the persistence of these two subsets in thymectomized mice. CD44(int) CD8 T cells persist like naive cells; i.e., they are slowly lost with time. However, surviving cells maintain their phenotype and memory characteristics for the entire life span of the animal. In contrast, CD44(high) CD8 T cells are persistent and accumulate in thymectomized but not euthymic mice. This is correlated with an increased in vivo proliferative and survival potential of these cells. These results show that acquisition of enhanced functional characteristics and long-term persistence by memory T cells are independent. This may have important consequences for the design of specific vaccine.
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PMID:Differential in vivo persistence of two subsets of memory phenotype CD8 T cells defined by CD44 and CD122 expression levels. 1188 36

Ly49 and CD94/NKG2 inhibitory receptors are predominantly expressed on murine NK cells, but they are also expressed on a subpopulation of peripheral CD8 memory TCR alphabeta lymphocytes. In this study we demonstrate that Ly49E and CD94/NKG2 receptors are expressed on mature TCR Vgamma3(+) cells in the fetal thymus. Expression correlated with a memory phenotype, such as expression of CD44, 2B4, and IL-2Rbeta (CD122), and absence of IL-2Ralpha (CD25) expression. No expression of Ly49A, C, D, G2, or I receptors was observed. This phenotype is similar to that of fetal thymic NK cells. Skin-located Vgamma3 T cells, the progeny of fetal thymic Vgamma3 cells, also expressed CD94/NKG2 and Ly49E but not the other members of the Ly49 family. The development and survival of Ly49E(+) or CD94/NKG2(+) Vgamma3 T lymphocytes was not dependent upon expression of MHC class I molecules. The cytotoxicity of TCR Vgamma3 cells was inhibited when Qdm, the ligand for CD94/NKG2, was presented by Qa1(b)-transfected target cells. Also, upon cross-linking of CD94/NKG2 with mAb 3S9, TCR Vgamma3 thymocytes were prevented from killing FcgammaR(+) P815 target cells. These effects were most pronounced in the CD94/NKG2(high) subpopulation as compared with the CD94/NKG2(low) subpopulation of Vgamma3 cells. Our data demonstrate that Vgamma3 T cells expressing inhibitory Ly49E and CD94/NKG2 receptors are mature and display a memory phenotype, and that CD94/NKG2 functions as an inhibitory receptor on these T lymphocytes.
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PMID:Expression of inhibitory receptors Ly49E and CD94/NKG2 on fetal thymic and adult epidermal TCR V gamma 3 lymphocytes. 1190 85

The most immature lymphoid-committed progenitors in both the bone marrow (common lymphoid progenitor) and thymus (proT1) maintain a latent granulocyte/macrophage (G/M) differentiation potential that can be initiated by signals emanating from exogenously expressed IL-2 receptors. In this study, we investigate at which developmental stage thymocytes lose this G/M differentiation potential. We demonstrate that the next maturational stage after proT1 cells (proT2), but not preT (TN3) cells, can convert cell fate from lymphoid to myeloid in response to ectopic IL-2 receptor signaling in human IL-2Rbeta transgenic mice. It is significant that approximately 10% of clonogenic G/M colonies derived from proT cells of IL-2Rbeta transgenic mice have DJ rearrangement specifically at the Dbeta1 but not Dbeta2 segment in the TCRbeta locus. No TCR gene rearrangement is observed in G/M cells from nontransgenic mice, suggesting that the G/M cells we observe in this system were truly lymphoid-committed before stimulation with IL-2. In addition, Dbeta1 and Dbeta2 DJ rearrangement of the TCRbeta gene may be differentially regulated and thus serve as markers for distinct proT cell maturational stages.
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PMID:Lineage infidelity in myeloid cells with TCR gene rearrangement: a latent developmental potential of proT cells revealed by ectopic cytokine receptor signaling. 1191 22

During T-cell development in thymus, CD25, the IL-2 receptor alpha chain (IL-2Ralpha) is already expressed in early double-negative (DN) thymocytes where commitment to T-cell lineage has been established, but subsequently IL-2Ralpha is dramatically down-regulated for the remainder of T-cell development. The loss of IL-2Ralpha expression after expression of the pre-TCR alpha:beta complex on the cell surface is essential for the later specific responses of mature T cells. Using appropriate mouse models and DMS genomic footprinting, we showed that the TATA box in the core promoter region of the murine IL-2Ralpha locus was occupied only in DN CD25+ T cells. Further, by chromatin immunoprecipitation assays, we evidenced that down-regulation of IL-2Ralpha transcription correlated with (i) loss of the basal transcriptional machinery; (ii) dissociation of histone acetylase p300 and BRG1, a member of the ATP-dependent chromatin remodeling complex SWI/SNF; and (iii) histone N-termini dephosphorylation plus deacetylation. In contrast, occupancy of the proximal enhancer region (positive regulatory region I) was not detected by in vivo genomic footprinting though constitutive accessibility of the promoter region for DNase I digestion both in the DN and double-positive stages correlated with the constitutive association of CBP and PCAF to the IL-2Ralpha core promoter. These results exemplify one mechanism by which a promoter enables transcription to switch on and off during T-cell differentiation.
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PMID:Control of IL-2Ralpha gene expression: structural changes within the proximal enhancer/core promoter during T-cell development. 1197 31

T lymphocytes are heterogeneous with respect to their ability to proliferate following activation in vitro and in vivo. Approximately 30% of T lymphocytes fail to progress through the cell cycle, despite showing evidence of an activated state. The population of T lymphocytes that remains undivided during a primary stimulation has been shown to be refractory to restimulation via the TCR and fails to proliferate in response to IL-2. In an in vitro model of T-cell deletion following clonal expansion, we demonstrate that T lymphocytes that do not progress through the cell cycle during primary stimulation have a sevenfold greater survival advantage compared with T lymphocytes that have divided. Progression through multiple division cycles is associated with down-regulation of Bcl-2 during a postactivation period of growth factor withdrawal. However this alone does not account for diminished survival, as constitutive expression of a Bcl-2 transgene did not restore survival to the levels seen in undivided cells. Engagement of the IL-2 receptor on these undivided activated T lymphocytes leads to enhanced survival and up-regulation of Bcl-2 and Bcl-xL. Surprisingly, while IL-2 also induces phosphorylation of Akt, it does not initiate cell cycle progression in this population of primary undivided cells. Our data provide evidence that a T cell's survival capacity is linked to its proliferative behavior. Furthermore, our results provide the first report of a population of T cells, in which the IL-2 receptor-mediated signaling pathways leading to survival and proliferation are naturally uncoupled.
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PMID:Interleukin-2-mediated survival and proliferative signals are uncoupled in T lymphocytes that fail to divide after activation. 1209 13

We investigated the individual CD8+ populations with natural killer (NK) cell markers (NK-type T cell); CD56 single positive (CD56)-T cells, CD56/CD57 double positive (DP)-T cells and CD57 single positive (CD57)-T cells in the peripheral blood. All NK-type T-cell populations expressed CD122 and intermediate levels of T-cell receptor (TCR; regular CD8+ T cells are CD122- and express high levels of TCR). The number of both DP-T cells and CD57-T cells, but not CD56-T cells, gradually increased with age. All NK-type T-cell populations produced larger amounts of interferon-gamma than did regular CD8+ T cells after stimulation with interleukin (IL)-2, IL-12 and IL-15. However, CD56-T cells and CD57-T cells but not DP-T cells showed a potent antitumour cytotoxity to NK-sensitive K562 cells, whereas only CD56-T cells showed a potent cytotoxity to NK-resistant Raji cells. Furthermore, although NK-type T cells produced large amounts of soluble Fas-ligands, their cytotoxic activities appeared to be mediated by the perforin/granzyme pathway. The oligoclonal or pauciclonal expansions of certain VbetaT cells were found in each NK-type T-cell population. The non-variant CDR3 region(s) for the TCRbeta chain(s) showed CD57-T cells and CD56-T cells to be derived from distinct origins, while the DP-T cell population consisted of a mixture of the clones seen in both CD56-T cells and CD57-T cells. Our results suggest that CD57-T cells and CD56-T cells are functionally and ontogenically different populations while DP-T cells appear to originate from both CD56-T cells and CD57-T cells.
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PMID:Functional and Vbeta repertoire characterization of human CD8+ T-cell subsets with natural killer cell markers, CD56+ CD57- T cells, CD56+ CD57+ T cells and CD56- CD57+ T cells. 1256 30

The existence and functions of muscarinic acetylcholine (mACh) receptors in human T lymphocytes were investigated. RT-PCR analysis demonstrated the presence of M(1) and M(2) subtypes of mACh receptors in human T lymphocytes. Pretreatment with oxotremorine-M (Oxo-M) caused the increase in phytohemagglutinin-induced IL-2 production. Since 4-DAMP suppressed Oxo-M-caused enhancement in IL-2 production, M(1) receptors seem to be involved in the enhancement of the production. Oxo-M stimulated IL-2 receptor mRNA expression and DNA synthesis. Our results suggest that muscarinic receptors, perhaps M(1) receptors are involved in the enhancement of TCR-induced IL-2 production and IL-2 receptor expression in human T lymphocytes. Thus muscarinic receptors positively modulate cell growth in human T lymphocytes by the autocrine mechanism through enhancing expression of both IL-2 and the receptors.
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PMID:The presence and functions of muscarinic receptors in human T cells: the involvement in IL-2 and IL-2 receptor system. 1262 67

The plasma membrane is compartmentalized into microdomains and the association/dissociation of receptors and signaling molecules with/from these membrane domains is a major principle for regulation of signal transduction. By following the reorganization of microdomains on living cells and performing biochemical studies, we show that Ab targeting of the T cell activation-associated Ag CD147 prevents TCR stimulation-dependent reorganization and clustering of microdomains. Triggering CD147 induces a displacement of the GPI-anchored coreceptors CD48 and CD59 from microdomains in human T lymphocytes. This perturbation of microdomains is accompanied by a selective inhibition of TCR-mediated T cell proliferation. The CD147-inhibited cells secret normal levels of IL-2 but acquire reduced amounts of the IL-2 receptor alpha-chain CD25. These results indicate that negative regulating signals can modulate microdomains and suggest a general mechanism for inhibition of receptor signaling.
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PMID:Selective inhibition of T cell activation via CD147 through novel modulation of lipid rafts. 1290 69

CpG oligodeoxynucleotide (ODN) promotes maturation of APCs in vivo and induces strong type 1 T cell responses in mice. In this study, we have investigated the ability of CpG1826 to modulate peptide-specific CD8 T cell responses in a context where CD4 T cells are likely to play a minor role. The effects of CpG1826 were evaluated in a system where a population of NP68-specific F5 TCR transgenic CD8 T cells is diluted into a polyclonal host following adoptive transfer into C57BL/10 syngeneic recipients. Using this approach, we found that CpG1826 enhanced the ability of F5 CD8 T cells to undergo multiple divisions in vivo, to express IFN-gamma ex vivo, and to up-regulate memory-associated cell surface markers such as CD122 (IL-2Rbeta) and Ly-6C. Moreover, CpG1826 greatly increased in vivo cytotoxic activity. Using tetramer detection, we found that CpG1826 promoted long-term survival of Ag-specific CD8 T cells after immunization while no NP68-specific cells were detected when the cognate peptide was injected alone. These results indicate that CpG1826 acts as an adjuvant which increases CD8 T cell effector responses and promotes long-term survival of NP68 peptide-specific cells in vivo. They also suggest that this adjuvant can modulate CD8 T cell responses in a system which is likely to be independent of CD4 T cell help.
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PMID:In vivo impact of CpG1826 oligodeoxynucleotide on CD8 T cell primary responses and survival. 1296 Mar 24

Selective isolation of only those CD4+ T cells that display the highest levels of CD25 by FACS results in a highly homogeneous regulatory population as defined by functional activity and the expression of multiple surface antigens. Thus greater than 98% of CD4+CD25high cells express CD45RO in the absence of CD45RA expression. Upon TCR stimulation CD4+CD25high cells are both anergic and tolerogenic as they inhibit proliferation and cytokine secretion by activated CD4+CD25- responder T cells in a contact-dependent manner. In contrast, CD4+ cells that express lower levels of CD25 are more heterogeneous in their levels of expression of CD45RO, HLA-DR and CD122, and do not exhibit anergic or suppressive characteristics. Providing either CD28 co-stimulation or IL2 to a maximal anti-CD3 stimulus results in a modest induction of proliferation and the loss of observable suppression by CD4+CD25high regulatory cells. Unlike CTLA4 blockade, blocking the interaction of PD-1 with its ligand PD-L1 affects the level of suppression. However, since this reduction in suppression by alphaPD-L1 can be overcome by increasing the number of CD4+CD25high T cells in the co-culture assay, the mechanism of CD4-CD25high regulation can proceed in the absence of PD-1/PD-L1 interactions, although it is not as efficient.
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PMID:CD4+CD25+ regulatory cells from human peripheral blood express very high levels of CD25 ex vivo. 1460 13


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