Intact T cell receptor signaling by CD4+ T cells cultured in the rotating wall-vessel bioreactor

D. M. Simons, E. M. Gardner, P. I. Lelkes

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

T lymphocytes fail to proliferate or secrete cytokines in response to T cell receptor (TCR) agonists during culture in spaceflight or ground-based microgravity analogs such as rotating wall-vessel (RWV) bioreactors. In RWVs, these responses can be rescued by co-stimulation with submitogenic doses of the diacyl glycerol (DAG) mimetic phorbol myristate acetate. Based on this result we hypothesized that TCR activation is abrogated in the RWV due to impaired DAG signaling downstream of the TCR. To test this hypothesis we compared TCR-induced signal transduction by primary, human, CD4+ T cells in RWV, and static culture. Surprisingly, we found little evidence of impaired DAG signaling in the RWV. Upstream of DAG, the tyrosine phosphorylation of several key components of the TCR-proximal signal was not affected by culture in the RWV. Similarly, the phosphorylation and compartmentalization of ERK and the degradation of IκB were unchanged by culture in the RWV indicating that RAS- and PKC-mediated signaling downstream of DAG are also unaffected by simulated microgravity. We conclude from these data that TCR signaling through DAG remains intact during culture in the RWV, and that the loss of functional T cell activation in this venue derives from the affect of simulated microgravity on cellular processes that are independent of the canonical TCR pathway.

Original languageEnglish
Pages (from-to)1201-1209
Number of pages9
JournalJournal of Cellular Biochemistry
Volume109
Issue number6
DOIs
StatePublished - Apr 15 2010
Externally publishedYes

Keywords

  • Activation
  • Lymphocyte
  • Microgravity
  • Signal transduction
  • Spaceflight

Fingerprint

Dive into the research topics of 'Intact T cell receptor signaling by CD4+ T cells cultured in the rotating wall-vessel bioreactor'. Together they form a unique fingerprint.

Cite this