Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epstein-Barr virus is associated with several human malignancies including Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's disease (HD). To examine the effect of Epstein-Barr virus nuclear antigen 1 (EBNA-1) in the pathogenesis of HD, we transfected the gene into the HD cell line L428. EBNA-1 expression was associated with significantly enhanced CD25 expression (interleukin 2 [IL-2]-receptor alpha chain) in transient and stably transfected L428 cells but did not affect the expression of IL-2 receptor beta and gamma chains. There was no up-regulation of the B-cell activation molecules CD23, CD30, CD39, CD40, CD44, CD71, and CD54 (intercellular adhesion molecule 1) or enhanced production of IL-6, IL-10, lymphotoxin alpha, and the soluble form of CD25. Stable EBNA-1-expressing L428 cells were nontumorigenic in SCID mice but showed enhanced lymphoma development in nonobese diabetic-SCID mice compared to mock-transfected cells.
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PMID:Expression of epstein-barr virus nuclear antigen 1 is associated with enhanced expression of CD25 in the Hodgkin cell line L428. 988 70

A previously undefined phenotype of CD8(+) cells that appears to represent in vivo activated CTL precursors (CTLP*) has been identified in the spleens of C57Bl/6 mice responding to a P815 tumor allograft. This population was first evident by the transient expression of very high levels of CD28 and CD44 on day 5 of the allograft response and reached maximal levels on days 7 and 8 before declining on day 9. A transient increase in CD69 expression was also observed on these cells on day 5. In contrast, CTL effectors (CTLE), identified by their CD8(+)CD44(hi)CD62LloCD45RBlo phenotype, were not appreciably detected in the spleen until day 8 and reached maximal levels on day 10. Further characterization of CTLP* on day 7 revealed that they represented blasting cells by increased light scatter and also expressed very high levels of CD54 but not CD122, CD152, or CD154. In addition, the cells had already up-regulated CD49d, asialo GM1, CD11a, and CD95L, and down-regulated their expression of CD62L. A small percentage of these cells also expressed CD25. Day 7 CTLP* sorted on the basis of their CD44(xhi) and CD54(xhi) phenotype did not exhibit cytolytic activity in a standard chromium release assay but became cytotoxic when they were cultured in the presence of exogenous murine IL-2 for 5 days. Granzyme B activity, however, was detected in CTLP* on day 7 at levels equivalent to CTLE on day 10. In order to establish a potential precursor relationship between CTLP* and CTLE, mice were treated with various doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a chemical that has been shown to dose-dependently suppress the in vivo generation of CTLE to P815 tumor cells by altering an early stage of CTLP activation. Results indicated that CTLP* were suppressed by TCDD on day 7 to the same degree that CTLE were suppressed on day 10. Importantly, for controls and for all doses of TCDD, there were approximately 12.5 CTLE on day 10 for every CTLP* detected on day 7. These results suggested that TCDD acted identically across all doses to inhibit the early stages of activation of CTLP but did not affect the final stages of differentiation and expansion to CTLE. This interpretation supports the previous observation that TCDD exposure had to occur within the first 3 days of the allograft response in order to induce suppression of CTLE activity. Taken together, these results support the conclusion that in vivo activated CTLP can be identified by their unique expression of very high levels of CD44, CD28, and/or CD54 prior to their full maturation and clonal expansion to functional CTLE.
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PMID:Novel phenotype associated with in vivo activated CTL precursors. 1007 61

To determine whether administration of G-CSF induces phenotypic or functional changes in T cells, we examined peripheral blood T cells from normal individuals receiving G-CSF for activation antigen and adhesion molecule expression before and after G-CSF administration. G-CSF (10 microg/kg/day) was administered subcutaneously to 14 normal individuals for 3-5 days and their PBMC were serially analyzed with monoclonal Ab (mAb) directed to HLA-DR, CD45RO, CD45RA, CD25, CD122, CD95, CD11a, CD49d, CD44 and CD62L (L-selectin) coupled with anti-CD3 mAb. Among T cells positive for these antigens, only the proportion of T cells expressing L-selectin significantly decreased from 68% to 37% after 3-day G-CSF administration. When peripheral blood CD3+ T cells obtained before and after G-CSF administration were sorted into two populations depending on the expression of L-selectin and tested for their proliferative response to allogeneic B cells, the reactivity of L-selectin- cells to alloantigen stimulation was consistently lower than that of L-selectin+ cells regardless of the exposure to G-CSF. The decrease in the relative number of L-selectin+ cells induced by G-CSF administration may contribute to the unexpectedly low incidence of severe acute GVHD after allogeneic PBSC transplantation.
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PMID:Administration of G-CSF to normal individuals diminishes L-selectin+ T cells in the peripheral blood that respond better to alloantigen stimulation than L-selectin- T cells. 1019 95

Class I MHC-restricted, HSV-1-specific CD8(+) cytolytic T lymphocyte (CTL) function is rarely detected in lymphocytes isolated directly from the lymph node draining the site of infection. However, culture in vitro for 24 to 72 h in the absence of exogenous antigen results in the development of easily detectable levels of HSV-1-specific CTL effectors. The inability to detect virus-specific CTL in HSV-1-infected mice is not well understood. However, since the in vitro culture of HSV-1-immune lymphocytes results in the transition to CTL function, studies of the changes occurring to the CD8(+) T cell subpopulation may provide important insights into the development of virus-specific CTL. Therefore, the phenotypic changes taking place in the CD8(+) population of T cells from draining popliteal lymph nodes of HSV-1-infected C57BL/6 (B6) mice were investigated, focusing on changes in the expression of cell surface markers associated with T lymphocyte activation. The results demonstrate an increase in the percentage of CD8(+) T cells expressing the activation markers CD44 and CD25 in parallel with the acquisition of HSV-specific CTL effector function. Cytolytic function was found exclusively within the CD8(+) CD44(hi) CD25(hi) fraction of cells in culture, but, surprisingly, was not detectable in CD8(+) CD44(hi) CD25(lo) T cells. This suggested that the acquisition of high levels of the high-affinity IL-2 receptor was closely linked to cytolytic function and may define an important developmental stage in the transition from noncytolytic to cytolytic effector cell. In support of this, CD8(+) CD25(hi) T cells isolated from the regional lymph node exhibited direct ex vivo cytolytic function, indicating that cytolytic effector cells were present in the lymph node, but must emigrate rapidly after attaining this level of differentiation.
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PMID:Phenotypic characteristics associated with the acquisition of HSV-specific CD8 T-lymphocyte-mediated cytolytic function in vitro. 1035 86

Optimal immunological control of cutaneous herpes simplex virus type 1 (HSV-1) infections initiated in the hind footpad of C57BL/6 (B6, H-2b) mice is dependent upon the presence of functional HSV-1-specific T lymphocytes. The class I MHC-restricted, CD8+ T cell subpopulation is involved in the clearance of infectious HSV-1 from the skin and limiting HSV-1 replication and spread within the peripheral nervous system. However, the frequency of HSV-1-specific CTL precursors (CTLp), as a measure of potential anti-viral CD8+ T cell function, is relatively low compared with other acute viral infections. To gain insight into the basis for this low functional frequency, changes in the CD8+ T cell subpopulation phenotype associated with activation and differentiation were investigated. Analysis of the phenotypic changes showed that HSV-1-specific CTLp were found predominantly within a subpopulation of CD8+ T cells expressing high levels of CD44 (CD44high) and high levels of the IL-2 receptor alpha-chain (CD25high). A second activated subpopulation of CD8+ T cells expressing the CD44high CD25low phenotype did not contain detectable HSV-1-specific CTLp, even after the addition of HSV-1-infected stimulator cells as a source of an exogenous Ag. These data suggested that HSV-1-specific CD8+ T cells must increase expression of CD25 before attaining the potential to become CTL effector cells. These findings also indicated that the up-regulation of CD44 alone is not sufficient to identify precisely HSV-1-specific CD8+ T cells.
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PMID:Phenotypic identification of antigen-dependent and antigen-independent CD8 CTL precursors in the draining lymph node during acute cutaneous herpes simplex virus type 1 infection. 1039 57

Through measurements of intracellular cytokine production, evidence is provided at the single cell level that triggering different cell surface molecules preferentially activates discrete human peripheral blood (PB) T cell subsets. T cell costimulation due to cross-linking a variety of individual molecules (beta1, beta2, and beta7 integrins, CD26, CD43, or CD44), in conjunction with the CD3/TCR complex, preferentially activated CD45RO+ PB T lymphocytes. CD28, however, costimulated interleukin-2 (IL-2) production in both CD45RO+ and CD45RA+ subpopulations. The amount of soluble IL-2 produced by CD28 coactivation was 15-30-fold higher than that due to integrin or CD26-dependent coactivation, although even the lowest amount of soluble IL-2 produced was in the range of the high-affinity IL-2 receptor. The overall proliferative responses were similar among all costimulatory settings. This was in part due to the uniform upregulation of IL-2 receptor-alpha (IL-2R alpha) (CD25) expression on the entire T cell population activated under each of the different costimulatory conditions. The data provide direct evidence on a single cell level that activation of human CD45RA+ (naive) T cells is stringently controlled and, in these studies, limited to CD28 costimulation for induction of IL-2 production. In contrast, coactivation of CD45RO+ (memory) T lymphocytes can proceed by a variety of different PB T cell surface molecules.
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PMID:Intracellular analysis of interleukin-2 induction provides direct evidence at the single cell level of differential coactivation requirements for CD45RA+ and CD45RO+ T cell subsets. 1045 48

Cultured murine CD4+ T cell lines from Saccharopolyspora rectivirgula-sensitized donors with cytokine secretion characteristics of Th1 cells can adoptively transfer murine experimental hypersensitivity pneumonitis (EHP), whereas Th2 CD4+ cell lines cannot (Cell Immunol 177:169-175, 1997). To assess the differences between these cell lines that may be related to the ability to transfer EHP, we determined cell surface markers that distinguish naive from activated/memory cells that indicate activation and that mediate endothelial adhesion. Both Th1 and Th2 T cell lines are CD4+, CD11a+, ICAM-1+, and L-selectin negative. Th1 cells are CD49d (alpha 4) and LPAM (alpha 4 beta 7) positive, with 32% and 42% of the apparent membrane site density quantitated as the mean molecules of equivalent soluble fluorochromes (MESF) values of unstimulated spleen cells, respectively. Th2 cells are weakly alpha 4 and alpha 4 beta 7 positive, with 15% and 11% of the MESF of unstimulated spleen cells. Th1 cell lines are CD45Rb negative and CD44+, whereas Th2 cell lines are CD45Rb intermediate and CD44-/low. Th1 cells are CD25 (IL-2 receptor) low and Th2 cells CD25 high. We conclude that Th1 cells capable of transfer are activated/memory T cells, and Th2 cells incapable of transfer lack some characteristics of memory/activated T cells (i.e., increase of CD44 and decrease of CD45Rb). Both Th1 and Th2 cell lines express alpha 4 beta 7 and alpha 4 (Th1 > Th2), suggesting that alpha(4) integrin may be important in conferring ability to cells to adoptively transfer EHP.
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PMID:Th1 cells that adoptively transfer experimental hypersensitivity pneumonitis are activated memory cells. 1054 88

We have established a new clonal assay system that can evenly support the development of T and natural killer (NK) cells. With this system, we show that all T cell progenitors in the earliest CD44(+)CD25(-)FcgammaRII/III(-) fetal thymus (FT) cell population retain NK potential, and that the NK lineage-committed progenitors (p-NK) also exist in this population. T cell lineage-committed progenitors (p-T), which are unable to generate NK cells, first appear at the CD44(+)CD25(-) FcgammaRII/III(+) stage in day 12 FT. The proportion of p-T markedly increases during the transition from the CD44(+)CD25(-) stage to the CD44(+)CD25(+) stage in day 14 FT. On the other hand, p-NK preferentially increase in number at the CD44(+)CD25(-) stage between days 12 and 14 of gestation. The production of p-NK continues up to the CD44(+)CD25(+) stage, but ceases before the rearrangement of T cell receptor beta chain genes. It was further shown that the CD44(+)CD25(-) CD122(+) population of day 14 FT exclusively contains p-NK. These results indicate that the earliest T cell progenitor migrating into the FT is T/NK bipotent, and strongly suggest that the bipotent progenitor continuously produces p-NK and p-T until the CD44(+)CD25(+) stage.
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PMID:Commitment of common T/Natural killer (NK) progenitors to unipotent T and NK progenitors in the murine fetal thymus revealed by a single progenitor assay. 1058 52

Intestinal intraepithelial lymphocytes (i-IEL) represent one of the largest, non-organized lymphoid population in the body. They are located outside the epithelial basement membrane among the mucosal epithelial cells. We, and previously other groups, have reported the presence of a CD7+CD3-IEL subset in the epithelium of human small intestine. This subset is drastically reduced in coeliac disease (CD) patients. In the present work we accomplish a better phenotypic characterization of this CD3-IEL subset and demonstrate the expression of typical natural killer (NK) cell markers. Most, if not all, CD3-CD7+ cells express NKPR1 (CD161)[98% +/- 2] and CD122[92% +/- 6]. In addition, a variable percentage express CD2[55% +/- 16], CD94[24% +/- 18], CD56[44% +/- 21] and CD16[12% +/- 4], however, no CD57 expression was observed. Moreover, these cells contain perforin granules[75% +/- 5], supporting a potential cytolytic ability. Regarding adhesion molecules, CD18 and CD44 expression is absent, which is consistent with a limited capacity of migration. Altogether, these data suggest the presence of intraepithelial NK cells in human intestinal epithelium, a compartment where cytotoxic effectors have not been clearly defined.
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PMID:Intestinal intraepithelial lymphocytes contain a CD3- CD7+ subset expressing natural killer markers and a singular pattern of adhesion molecules. 1088 77

This study shows that naive CD8 T cells can acquire characteristics of memory T cells in the absence of stimulation with specific Ag simply by the process of homeostatic proliferation under lymphopenic conditions. This Ag-independent T cell differentiation pathway did not result in up-regulation of early activation markers (CD69, CD25, CD71), but expression of several memory markers (CD44, CD122, Ly6C) increased progressively with successive divisions. These markers were then stably expressed, and these cells also became more responsive functionally to specific Ag. Thus, all "memory" phenotype T cells in an individual may not be true Ag-experienced cells and may include naive cells masquerading as memory cells. These findings are specially relevant in cases of disease or treatment-induced lymphopenia such as in HIV-infected individuals or transplant recipients. In addition, this study may have implications for autoimmunity because homeostatic proliferation of naive T cells requires interaction with self peptide plus MHC molecules.
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PMID:Cutting edge: naive T cells masquerading as memory cells. 1092 49


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