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

GammadeltaT cells play a regulatory role in both primary and metastatic tumor growth in humans. The mechanisms responsible for the activation and proliferation of circulating gammadeltaT cells should be fully understood prior to their adoptive transfer to cancer patients. We have examined in vitro functional effects of interleukin-15 (IL-15) on highly purified gammadeltaT cells isolated from glioblastoma patients. GammadeltaT cells constitutively express the heterotrimeric IL-2 receptor (IL-2R) alpha betagamma, but the levels of IL-2Rbeta or gamma expression were not increased by incubation with saturating amounts of IL-15. IL-15 was shown to induce a maximal gammadeltaT cell proliferation, although at much higher concentrations (at least 2000 U/ml) than IL-2 (100 U/ml). Submaximal concentrations of IL-15 plus low concentrations of IL-2 produced an additive proliferative response. In contrast to the IL-2-induced response, this activity was completely or partially abrogated by anti-IL-2Rbeta, or anti-IL-2Rgamma antibodies, but not by anti-IL-2R alpha antibodies. Incubation of gammadeltaT cells in the presence of IL-15 resulted not only in the appearance of NK and LAK activity, but also in specific autologous tumor cell killing activity, an additive effect being seen with IL-15 and IL-2. This IL-15-induced tumor-specific activity could be significantly blocked by anti-IL-2Rgamma and anti-IL-2R-beta mAb, but not by anti-IL-2R alpha mAb. Thus, in contrast to IL-2, IL-15 activates tumor-specific gammadeltaT cells through the components of IL-2Rbeta and IL-2Rgamma, but not IL-2R alpha. These enhanced in vitro tumor-specific and proliferative responses of gammadeltaT cells seen with IL-15 suggest a rational adjuvant imunotherapeutic use of gammadeltaT cells in cancer patients.
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PMID:Interleukin-15 effectively potentiates the in vitro tumor-specific activity and proliferation of peripheral blood gammadeltaT cells isolated from glioblastoma patients. 976 18

Defects in innate immunity have been demonstrated in astronauts after space flight. To investigate the role of microgravity on innate immune function, we evaluated NK and LAK activity of human PBMC stimulated with IL-2 under conditions of simulated microgravity, by using a rotating wall vessel (RWV) culture system. Under these conditions, both NK and LAK activity were generated at levels comparable to those found in static flask cultures. The phenotype of the activated PBMC was similar between the two culture conditions, with one notable exception: the IL-2 receptor alpha chain (CD25), which failed to be upregulated in simulated microgravity. To further investigate this change in IL-2 signaling, we examined the ability of IL-2 to induce secondary cytokines. The production of IFNgamma, IL-1beta, and TNFalpha was almost completely abrogated in the microgravity cultures, suggesting that the IL-2 signaling pathways leading to various IL-2-mediated effects are differentially regulated under bioreactor culture conditions.
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PMID:Multiple interleukin-2 signaling pathways differentially regulated by microgravity. 1059 84

In the present study, we analyzed the proliferation and cytotoxic activities of LAK cells and initial phase TILs by stimulation with IL-4. IL-4 obviously inhibited the DNA synthesis of LAK cells and initial phase TILs at the concentration of 250 pg/ml and 25 pg/ml, respectively. Furthermore, IL-4 (25 ng/ml for LAK cells, 25 pg/ml for initial phase TILs) suppressed the cytotoxic activities against K562, KATO-III, and autologous tumor cells. The discrepancy of the concentration between the proliferation and the cytotoxicicity by IL-4 suggested different pathways in terms of the generation of LAK cells. In order to clarify the inhibitory mechanism of IL-4, we measured the expression of IL-2 receptor. IL-2 receptor alpha chain was strongly down-regulated by IL-4. Thus, IL-4 modulates the activation of LAK cells and initial phase TILs via the IL-2 receptor alpha chain.
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PMID:Interleukin-4 inhibits lak and initial phase til activity via interleukin-2 receptor. 2155 40


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