CD28 costimulation augments IL-2 secretion of activated lamina propria T cells by increasing mRNA stability without enhancing IL-2 gene transactivation
| Autor: | R, Gonsky, R L, Deem, D H, Lee, A, Chen, S R, Targan |
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| Rok vydání: | 1999 |
| Předmět: |
Transcriptional Activation
Transcription Genetic CD2 Antigens Nuclear Proteins Lymphocyte Activation Response Elements Transcription Factor AP-1 Mice Adjuvants Immunologic CD28 Antigens T-Lymphocyte Subsets Leukocytes Mononuclear Animals Humans Interleukin-2 RNA Messenger Intestinal Mucosa Plasmids Protein Binding Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 162(11) |
| ISSN: | 0022-1767 |
| Popis: | The pathways leading to activation in lamina propria (LP) T cells are different from peripheral T cells. LP T cells exhibit enhanced IL-2 secretion when activated through the CD2 pathway. Coligation of CD28 leads to synergistic enhancement of IL-2 secretion. Previous studies have characterized the CD28 augmentation of TCR-mediated signaling in peripheral blood T cells through transcriptional activation of an IL-2 promoter CD28 response element (CD28RE), along with enhanced mRNA stability. This study characterized molecular events involved in CD28 costimulation of IL-2 production in LP mononuclear cells (LPMC). LPMC exhibited increased IL-2 production in response to CD28 costimulation, compared with cells activated through CD2 alone. IL-2 secretion was paralleled by increased expression of IL-2 mRNA, resulting from enhanced IL-2 mRNA stability. In contrast to transcriptional activation in PBMC, EMSA revealed that CD28 coligation of CD2-activated LPMC does not result in increased binding of trans-factors to the CD28RE, nor did Western blots detect changes in I-kappaBalpha or I-kappaBbeta levels following CD28 coligation. Furthermore, CD28 coligation fails to enhance IL-2 promoter-reporter or RE/AP construct expression in CD2-activated LPMC. The results reported herein indicate that the molecular mechanisms involved in CD28 cosignaling and regulation of IL-2 secretion in LP T cells are unique to that compartment and differ from those seen in peripheral blood T cells. These observations suggest a biological significance for different mechanisms of IL-2 activation in initiation and maintenance of the cytokine repertoire found in the mucosa. |
| Databáze: | OpenAIRE |
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