Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transgenic mice carrying the human IL-2R alpha/p55 gene under the control of the SV40 enhancer/promoter were used to study the relevance of IL-2R in T-cell development. Serological analysis of the mouse lines obtained indicated transient, regulated expression of the human p55 gene, mainly confined to the early thymus, but which was also detected in lower amounts in the spleen. These mice showed degenerated thymuses, with an increased number of Thy1.2- double-negative precursor cells; they also had specific depletion of double-positive thymocytes. Transgene expression led to an increased number of intermediate-affinity IL-2 receptors (possibly ascribed to deregulated expression of IL-2R beta/p75) in transgenic thymocytes older than 12 weeks. These results suggest the occurrence of strong linkage between the IL-2/IL-2R system elements and thymic differentiation/maturation; they lend support to the idea of functionality of IL-2R expressed transiently in early stages of T-cell development.
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PMID:Analysis of T-cell subpopulations in human IL-2R alpha transgenic mice: expansion of Thy1.2- thymocytes and depletion of double-positive T-cell precursors. 257 90

Delayed lymphocyte infusions (DLIs) are used to treat relapse occurring post bone marrow transplantation (BMT) and to increase the donor chimerism in recipients receiving nonmyeloablative conditioning. As compared with donor lymphocytes given early post-BMT, DLIs are associated with a reduced risk of graft-vs-host disease (GVHD). The mechanism(s) responsible for such resistance have remained incompletely defined. We now have observed that host T cells present 3 wk after lethal total body irradiation, at the time of DLI, contribute to DLI-GVHD resistance. The infusion of donor splenocytes on day 0, a time when host bone marrow (BM)-derived T cells are absent, results in greater expansion than later post-BMT when host and donor BM-derived T cells coexist. Selective depletion of host T cells with anti-Thy1 allelic mAb increased the GVHD risk of DLI, indicating that a Thy1(+) host T cell regulated DLI-GVHD lethality. The conditions by which host T cells are required for optimal DLI resistance were determined. Recipients unable to express CD28 or 4-1BB were as susceptible to DLI-GVHD as anti-Thy1 allelic mAb-treated recipients, indicating that CD28 and 4-1BB are critical to DLI-GVHD resistance. Recipients deficient in both perforin and Fas ligand but not individually were highly susceptible to DLI-GVHD. Recipients that cannot produce IFN-gamma were more susceptible to DLI-GVHD, whereas those deficient in IL-12 or p55 TNFRI were not. Collectively, these data indicate that host T cells, which are capable of generating antidonor CTL effector cells, are responsible for the impaired ability of DLI to induce GVHD. These same mechanisms may limit the efficacy of DLI in cancer therapy under some conditions.
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PMID:Host T cells resist graft-versus-host disease mediated by donor leukocyte infusions. 1104 15