Cellular interactions in the thymus regulate the protein kinase C signaling pathway

Porritt, Helen E.; Anderson, Kim L.; Suniara, Ravinder K.; Jenkinson, Eric J.; Owen, J. J. T.

doi:10.1002/(sici)1521-4141(199804)28:04<1197::aid-immu1197>3.0.co;2-n

Cited by 7 publications

(3 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the thymus it is likely that interactions between thymocytes and stromal cells induce not only an increase in [Ca 2ϩ ] i but also other signals including those that activate protein kinase C and those that suppress the protein kinase C signaling in thymocytes through TCR and accessory molecules (61,62). The net signals may determine the fate of each thymocyte.…”

Section: Cd8mentioning

confidence: 99%

Successive Expression and Activation of NFAT Family Members during Thymocyte Differentiation

Adachi¹,

Amasaki²,

Miyatake³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

Differentiation of immature CD4؉ CD8 ؉ thymocytes to mature CD4 ؉ or CD8 ؉ T cells is induced by positive selection and appears to involve calcineurin-dependent activation of NFAT, a family of transcription factors. NFATx is predominantly expressed in CD4 ؉ CD8 ؉ thymocytes, whereas NFATp and NFATc are expressed at much lower levels in the thymus than in mature T cells. However, how or when each NFAT member is involved in the differentiation pathway is unclear. Using an in vitro model system where isolated CD4 ؉ CD8؉ thymocytes can survive and differentiate into semi-mature CD4-lineage T cells, we suggest that low calcineurin activity sustained for approximately 20 h is required for cell survival and differentiation. Accordingly, the DNA binding activity of NFAT slowly increased during the stimulation of 20 h to induce the differentiation. NFATx significantly contributed to the early rise, but the late increase was mostly due to NFATc activation. Meanwhile, the expression of NFATx mRNA decreased and that of NFATc mRNA increased. The DNA-binding activity of NFATp was detectable but low throughout the stimulation. NFATp became dominantly active after the semi-mature T cells differentiated into mature and activated CD4 T cells. These findings suggest that NFATx and NFATc successively play roles in T cell development.

show abstract

Section: Cd8mentioning

confidence: 99%

Successive Expression and Activation of NFAT Family Members during Thymocyte Differentiation

Adachi¹,

Amasaki²,

Miyatake³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Indeed, in thymus organ cultures phorbol esters/ionophores cause downregulation of CD4 alone as opposed to downregulation of both coreceptors induced by antigen. 39 Furthermore phorbol ester/ionophores do not induce death in thymic organs whereas antigen does (data not shown and 39 ). Our findings concerning the selective defect in PKCe in DP thymocytes could account for the lack of NF-kB activity in response to antigen as phorbol esters/ionophores may use other PKC isoforms to signal.…”

Section: Discussionmentioning

confidence: 87%

The lack of NF-κB transactivation and PKCε expression in CD4+CD8+ thymocytes correlates with negative selection

et al. 2000

View full text Add to dashboard Cite

Deletion of autoreactive thymocytes at the DP stage is the basis for tolerance to thymus-expressed self antigens. In this study we investigated whether distinct signalling pathways are induced in DP thymocytes as compared to mature T cells upon stimulation with antigen. Using triple transgenic mice expressing a TCR transgene, dominant negative ras/Mek proteins and a reporter gene construct with AP-1 or NF-kappa B binding sites, we showed a complete lack of transcriptional activity of NF-kappa B but not AP-1 in DP thymocytes, whereas both were transcriptionally active in mature T cells after antigenic stimulation. Lack of NF-kappa B induction correlated with increased death in response to antigen. AP-1 induction was dependent on the integrity of the ras/Mek pathway indicating that this pathway was activated in the DP thymocytes. In contrast, we found a complete lack of constitutive expression of the epsilon isoform of Protein Kinase C (PKC) in DP thymocytes, although it was present in mature thymocytes and peripheral T cells. Taken together the results suggest that the lack of PKC epsilon in DP thymocytes could lead to the absence of NF-kappa B activity after antigenic stimulation contributing to negative selection. Cell Death and Differentiation (2000) 7, 1253 - 1262.

show abstract

“…Alterna-tively, in contrast to cell suspension cultures, thymocytes from intact thymic lobes interact with other cell types of the thymic microenvironment and consequently receive a different set of signals compared to those in suspension. Indeed, Anderson and colleagues observed a major difference in the utilization of the PKC pathway when thymocytes are stimulated with PMA in cell suspension compared to cells maintained within intact lobes [17].…”

Section: Discussionmentioning

confidence: 99%

Somatostatin is expressed in the murine thymus and enhances thymocyte development

2002

View full text Add to dashboard Cite

A functional interaction between the immune and the nervous system has been suggested, with neuropeptides acting as immunomodulators. Somatostatin (SOM) is a neuropeptide, mainly produced in the brain, that binds to five different receptors (SSTR). It is believed that SOM along with one of its receptors, SSTR2, is expressed in the murine thymus, although their exact localization is unresolved. We found that SOM is highly expressed in both cortical and medullary epithelial cells whereas its receptor SSTR2 is expressed on thymocytes. In order to elucidate its role in thymopoiesis, SOM was added in fetal thymic organ culture (FTOC) and found to increase thymocyte numbers and enhance maturation. SOM increased the cellular proliferation of total splenocytes but inhibited proliferation of thymocytes and purified splenic T cells. Furthermore, SOM was able to induce the migration of thymocytes. We also investigated the effect of four other neuropeptides in FTOC and found that, vasoactive intestinal peptide had a marginal effect, whereas substance P increased thymic cellularity, at intermediate but not at low or high concentrations. In contrast, both neuropeptide Y and calcitonin gene‐related peptide reduced thymocyte numbers. This study supports the hypothesis for a role of neuropeptides, particularly somatostatin, in immune regulation and development.

show abstract

Cellular interactions in the thymus regulate the protein kinase C signaling pathway

Cited by 7 publications

References 23 publications

Successive Expression and Activation of NFAT Family Members during Thymocyte Differentiation

Successive Expression and Activation of NFAT Family Members during Thymocyte Differentiation

The lack of NF-κB transactivation and PKCε expression in CD4+CD8+ thymocytes correlates with negative selection

Somatostatin is expressed in the murine thymus and enhances thymocyte development

Contact Info

Product

Resources

About