Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two interleukin 5 (IL5)-specific retroviral expression vectors have been constructed containing the neomycin gene as selectable marker and either the mouse IL5 cDNA region or the rat genomic IL5 gene under the control of the thymidine kinase promoter. High viral titer supernatants derived from the transfected or infected packaging cell line psi 2 were used to infect the two cell lines B13 and T88M whose growth is dependent on exogenous IL 5. Infection resulted in G418 resistance and IL 5-independent growth with a high frequency. Clones were established which secrete between 2 and greater than 1000 U IL5. The proliferation of the IL5 autocrine growing cells could be inhibited by an antibody directed against the IL5 receptor indicating that they grow as a result of the endogenously produced IL5. Regardless of the amount of IL5 they produced, all of the clones were highly tumorigenic in nucle mice. The phenotype of the tumors was indistinguishable from that of the injected cells. T88M or B13 cells infected with a control virus neither produced IL5, nor became factor independent, nor produced tumors. Together, the IL5 gene transfer and expression into IL5-dependent growing cells are in accordance with the "autocrine growth" hypothesis and contrast analogous experiments with IL4.
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PMID:Retroviral interleukin 5 gene transfer into interleukin 5-dependent growing cell lines results in autocrine growth and tumorigenicity. 226 30

A murine model of genital infection with a thymidine kinase-deficient (tk-) strain of herpes simplex virus type 2 (HSV-2) was utilized to examine the development of the local T cell response in the genital mucosa and draining genital lymph nodes (gLN). HSV-specific cytokine-secreting T cells were detected in the gLN 4 days postintravaginal inoculation but not in the urogenital tract or spleen until 5 days postinoculation, suggesting the cellular immune response originates in the gLN. More CD4+ than CD8+ gLN T cells were detected by flow cytometric analysis following primary vaginal inoculation and the majority of HSV-specific gLN T cells detected by ELISPOT were CD4+ and Th1-like based on secretion of IFN gamma and not IL-4 or IL-5. A similar population of HSV-specific memory T cells persisted in the genital tract 2 months following HSV-2 tk- genital inoculation. These data suggest that the urogenital cellular immune response elicited in mice following genital inoculation with HSV-2 tk- is predominantly CD4+ and Th1-like, resembling that observed in humans. The results of this study are important for the rational design of vaccines capable of inducing protective immunity in the genital tract.
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PMID:Analysis of herpes simplex virus-specific T cells in the murine female genital tract following genital infection with herpes simplex virus type 2. 757 18

Neonates are highly susceptible to HSV. In this study, we analyzed the primary neonatal cell-mediated response to HSV at the site of T cell activation, the draining lymph nodes (LN), and examined the effects of dose and the ability of HSV to replicate on the strength and character of this response. Neonatal mice mounted a predominantly Th1 cytokine (IFN-gamma) response at all doses of a replication-competent thymidine kinase-negative HSV-2 strain (186DeltaKpn) and at high doses of a replication-defective HSV-2 virus (dl5-29, UL5(-)/UL29(-)). Both neonates and adults showed increased production of Th2 cytokines (IL-4 and/or IL-5) at high doses of the replication-defective or inactivated HSV strains. An age-dependent difference in the strength of the Th1 response was noted, with neonates mounting adult-like responses at low but not high doses of HSV. Neonatal mice also showed impaired CD8(+) T cell activation and reduced HSV-specific CTL effector function at the time of the peak adult response. These studies are the first to highlight the impaired primary neonatal T cell response to HSV in the LN.
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PMID:HSV induces an early primary Th1 CD4 T cell response in neonatal mice, but reduced CTL activity at the time of the peak adult response. 1578 59