Accession Number : ADA539633


Title :   Evaluation of NF-kappaB Signaling in T Cells


Descriptive Note : Doctoral thesis


Corporate Author : UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD


Personal Author(s) : Kingeter, Lara M


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a539633.pdf


Report Date : Jan 2009


Pagination or Media Count : 72


Abstract : T cell activation of the transcription factor NF-kB is a tightly controlled process and many of the proteins involved in this signal transduction pathway have been identified. The proteins PKCtheta, Bcl10, and Malt1 are known to play a role in the T cell receptor (TCR) mediated activation of NF-kB, but the precise role of these proteins has not been characterized. To better understand the function of PKCtheta, Bcl10, and Malt1 in this pathway, we examined NF-kB activation in T cells deficient in these proteins. Our results show that the loss of PKCtheta, Bcl10, or Malt1 differentially affects CD4+ and CD8+ T cells. Knock-out CD4+ T cells showed a severe defect in proliferation, upregulation of activation markers, and phosphorylation of IkBalpha (a surrogate marker of NF-kB activation) in response to TCR ligation. In contrast, CD8+ T cells were only slightly impaired in proliferation and IkBalpha phosphorylation, and showed nearly normal upregulation of activation markers, especially in response to strong TCR stimulus. Taken together, these data indicate differences in the way mature CD4+ and CD8+ T cells signal to NF-kB, and suggest that in the absence of PKCtheta Bcl10, or Malt1, CD8+ T cells utilize a parallel pathway to activate NF-kB under conditions of strong TCR stimulation.


Descriptors :   *STIMULATION(PHYSIOLOGY) , *T LYMPHOCYTES , PHOSPHORYLATION , TRANSDUCERS , SENSE ORGANS , THESES , PROTEINS , PRECISION


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE