Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although tumor necrosis factor-alpha (TNF) is constitutively expressed in human and mouse thymus, the effects of TNF on thymocyte proliferation, differentiation and survival suggest that its influence in the thymus is complex. To determine if this complexity results from changes in the expression of the two TNF receptors during thymocyte differentiation, we examined the expression of the 55 kDa TNF receptor (TNF-R1) and the 75 kDa TNF receptor (TNF-R2) on postnatal human thymocytes. Both TNF-R1 and TNF-R2 mRNA were found in resting human thymocytes by reverse transcriptase-polymerase chain reaction (RT-PCR). Using mAb which specifically react with the respective TNF receptors and a highly sensitive, three-step method of immunofluorescence, cell surface TNF-R1 was detected on the vast majority of thymocytes. In contrast, detectable cell surface TNF-R2 was present on a mean of only 12.9% of thymocytes. TNF conjugated to phycoerythrin (TNF-PE) also reacted with a small population of thymocytes and was found to specifically block binding of the TNF-R2 mAb and not the TNF-R1 mAb, implicating preferential binding of TNF-PE to TNF-R2. Using dual-color immunofluorescence with TNF-PE we found that the population of cells which express TNF-R2 also express high levels of the TCR alpha, beta-CD3 complex, CD4 or CD8, and IL-2 receptor alpha chain. Thus, immature (TCRneg/low) thymocytes express TNF-R1 while mature (TCRhigh) thymocytes can also express TNF-R2. This differential expression of TNF receptors provides a mechanism for distinct effects of TNF on immature vs. mature thymocytes.
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PMID:Characterization of TNF receptors on human thymocytes. 852 4

CD8 memory T cells are enriched in the bone marrow, a site where these cells are thought to receive homeostatic signals. However, the primary site where CD8 memory T cells receive their cytokine-induced homeostatic signals has recently come under debate. In this study, we demonstrate that the bone marrow contains a fraction of CD8 memory phenotype T cells with elevated expression of glucocorticoid-induced TNFR-related protein (GITR). In contrast, splenic and lymph node memory phenotype T cells have GITR levels similar to those on naive T cells. The bone marrow GITR(hi) memory T cells have a phenotype indicative of cytokine activation, with higher CD122 and lower CD127 than do the GITR(basal) memory T cells. Remarkably, these bone marrow-specific GITR(hi) cells are almost completely ablated in the absence of IL-15, whereas TNFR2 and 4-1BB expression on the CD8 memory T cells are IL-15 independent. Furthermore, adoptively transferred splenic CD8 memory phenotype T cells show IL-15-dependent GITR upregulation upon entry into the bone marrow. This result implies that the selective appearance of GITR(hi) memory phenotype T cells in the bone marrow reflects the local microenvironment rather than a different subset of memory T cells. GITR(-/-) mice have a lower frequency of CD8 memory phenotype cells in the bone marrow, yet the GITR(-/-) cells hyperproliferate compared with those in wild-type mice. Taken together, these data suggest that GITR plays a role in the survival of CD8 memory phenotype T cells and that GITR upregulation represents a precise marker of cells that have responded to IL-15.
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PMID:IL-15-dependent upregulation of GITR on CD8 memory phenotype T cells in the bone marrow relative to spleen and lymph node suggests the bone marrow as a site of superior bioavailability of IL-15. 2258 58