Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early immune reconstitution after intensive chemotherapy for acute myelogenous leukemia (AML) occurs after 2-4 weeks of cytopenia, but T cell reconstitute is usually completed after several months. Interleukin-7 (IL-7) is a T cell growth factor involved in the late immune reconstitution, but its function during the early period of cytopenia has not been investigated. In the present study, we found that patients with untreated AML had decreased IL-7 serum levels, and induction chemotherapy had divergent effects on these levels. In contrast, patients in complete remission (CR) had intermediate levels immediately before consolidation therapy, and these levels decreased significantly when the patients developed therapy-induced cytopenia. Systemic IL-7 levels showed only minor increases during febrile neutropenia. Furthermore, IL-7 enhanced in vitro proliferative responses of polyclonal T cells derived from cytopenic patients, and the majority of circulating clonogenic CD4(+) and CD8(+) T cells from cytopenic patients could respond to both IL-2 and IL-7. To conclude, patients with untreated AML and severe chemotherapy-induced leukopenia (1) differ from other patients with CD4(+) T lymphopenia in that they show decreased IL-7 serum levels, and (2) the detection of circulating IL7-responsive T cells indicates that variations in systemic IL-7 levels are functionally important and contribute to an additional qualitative T cell defect in these severely T lymphopenic patients.
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PMID:Interleukin-7 (IL-7) in patients receiving intensive chemotherapy for acute myelogenous leukemia: studies of systemic IL-7 Levels and IL-7 responsiveness of circulating T lymphocytes. 1243 86

Aging is broadly defined as a progressive decline of tissue and organ functions due to deregulation of various cell intrinsic and extrinsic factors. In the immune system, aging preferentially affects lymphopoiesis and thus results in the reduced competence of the adaptive immune system in the elderly. Despite recent discoveries that shed light on the molecular basis of aging, pathways that lead to diminished lymphoid development in aging individuals remain largely unknown. In the present study, we document that a deficiency of the E3 ubiquitin ligase c-Cbl in lymphocytes results in an age-dependent lymphopenia. c-Cbl-deficient mice show normal frequencies of lymphocytes at 12 weeks of age; however, their development and functions were remarkably diminished at 24 weeks after birth. Intriguingly, c-Cbl mutant lymphocytes displayed increased responses to IL7 in vitro and failed to down-regulate surface levels of IL7Ralpha. Further, our biochemical studies have identified an interaction of c-Cbl with IL7Ralpha and have unraveled the involvement of c-Cbl in the ubiquitylation of IL7Ralpha. In essence, our studies demonstrate that a lack of signaling events mediated by c-Cbl might result in diminished lymphocyte development and functions, particularly, at the later stages of life.
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PMID:c-Cbl deficiency leads to diminished lymphocyte development and functions in an age-dependent manner. 2040 56