Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diverse clinical presentations of cutaneous T cell lymphoma (CTCL) have been unified by immunologic characterization of the malignant T cells as an expansion of clonal, CD4+ inducer T cells with affinity for epidermal association with Langerhans cells (LC), an immature member of the dendritic cell (DC) family. Features of the life cycle of CTCL have recently been elucidated through development of an in vitro cell culture system. In this system, the proliferation and survival of the CTCL cells is tied to an association with immature monocyte-derived DC. Growth of the CTCL cells requires direct contact with the DC and both cell types survive in the presence of supportive cytokines for 3 months. Separation of the CTCL cells and the DC, or DC maturation truncates the synergy between the two cell populations and results in rapid death of both cell types. The CTCL cells perpetuate DC immaturity and survival through secretion of interleukin 10 (IL10) and transforming growth factor-beta (TGF-beta). The immature DC are aggressively phagocytic and can engulf apoptotic CTCL cells that have exhausted their proliferative potential and present peptides derived from the apoptotic material in class II MHC molecules to the T cell receptor (TCR) of the CD4+ CTCL cell. CTCL cells are induced to become T-regulatory (Treg) cells when their TCR is triggered by DC class II presentation of peptides derived from apoptotic material. Treg CTCL cells suppress immune responses and secrete IL10 and TGF-beta, cytokines that perpetuate DC immaturity, providing continued opportunity for DC stimulation of CTCL cell growth. Understanding the CTCL cell life cycle unveils a variety of potential targets that can be exploited for therapeutic intervention.
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PMID:The life cycle of cutaneous T cell lymphoma reveals opportunities for targeted drug therapy. 1557 18

CD4(+) recent thymic emigrants (RTEs) comprise a clinically and immunologically important T cell population that indicates thymic output and that is essential for maintaining a diverse alphabeta-T cell receptor (TCR) repertoire of the naive CD4(+) T cell compartment. However, their frequency and function are poorly understood because no known surface markers distinguish them from older non-RTE naive CD4(+) T cells. We demonstrate that protein tyrosine kinase 7 (PTK7) is a novel marker for human CD4(+) RTEs. Consistent with their recent thymic origin, human PTK7(+) RTEs contained higher levels of signal joint TCR gene excision circles and were more responsive to interleukin (IL)-7 compared with PTK7(-) naive CD4(+) T cells, and rapidly decreased after complete thymectomy. Importantly, CD4(+) RTEs proliferated less and produced less IL-2 and interferon-gamma than PTK7(-) naive CD4(+) T cells after alphabeta-TCR/CD3 and CD28 engagement. This immaturity in CD4(+) RTE effector function may contribute to the reduced CD4(+) T cell immunity observed in contexts in which CD4(+) RTEs predominate, such as in the fetus and neonate or after immune reconstitution. The ability to identify viable CD4(+) RTEs by PTK7 staining should be useful for monitoring thymic output in both healthy individuals and in patients with genetic or acquired CD4(+) T cell immunodeficiencies.
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PMID:Human CD4+ T cell recent thymic emigrants are identified by protein tyrosine kinase 7 and have reduced immune function. 1917 67