Induction of CD4+ T cell apoptosis as a consequence of impaired cytoskeletal rearrangement in UVB-irradiated dendritic cells.

摘要: Low dose UVB irradiation of dendritic cells (DC) dose-dependently decreases their allostimulatory capacity and inhibits alloreactive T cell proliferation. The reduction the stimulatory is not associated with a perturbation CD28 costimulation. To examine underlying mechanism, cycle analysis from cocultures UVB-irradiated DC (UVB-DC) was performed, revealing no arrest, but an increased number apoptotic in sub-G 0 phase. We confirmed to undergo apoptosis after coincubation UVB-DC by TUNEL staining DNA laddering. analyze whether requires Fas/Fas ligand (FasL) pathway, MLRs were performed Fas-, FasL-deficient, wild-type cells. No differences found on comparison Fas-/FasL-deficient or Likewise, addition neutralizing anti-TNF-α mAb could overcome inhibition proliferation UVB-DC, excluding involvement TNF-α/TNF-αR pathway. FACS CD69 CD25 revealed up-regulation cocultured suggesting early activation. Analysis confocal microscopy demonstrated impaired filamentous actin bundling, process critical for stimulation. investigate functional relevance these observations, time lapse video performed. Indeed, calcium signaling CD4 + significantly diminished interaction UVB-DC. In conclusion, UVBR impairs cytoskeletal rearrangement induces disruption DC-T interaction, resulting reduced Ca 2+ influx