Abstract
(Englisch)
|
Initiation of immune responses: Cells and molecules decisive in innate immunity The transcription factor ReIB had been shown to be important for dendritic cell (DC) development, but the type of DC involved was not clear. RelB mRNA was found to be strongly expressed in CD8a- DEC-205- DC but only weakly in CDa+ DEC-205+ DC. In addition, CD8a+( DEC-205+ DC are present and functional in RelB null mice, the DC deficiency being mainly in the CD8a- DEC-205- population. By constructing bone - marrow chimeric mice, we demonstrate that the partial deficiency in RelB null thymic mice is a secondary effect of disrupted thymic architecture. However, the deficiency in splenic CD8a- DEC-205- is a direct, stem cell intrinsic effect of the RelB mutaUon. Thus, RelB selectively regulates a myeloid -related DC lineage.
· Cytotoxic T lymphocytes (CTL) and NK cells are critical effectors of antitumor immune responses in vivo. Since dendritic cells (DC) prime tumor antigen -specific CTL, we addressed whether DC might also trigger the innate, NK cell -mediated antitumor immunity. In MHC class I - negative tumor - bearing mice, we show that adoptive transfer or Flt3 ligand - induced expansion of DC promoted NK cell dependent antitumor effects. In vitro studies demonstrate a cell to cell contact between DC and resting NK cells resulting in dramatic increase in both NK cell cytolytic activity and IFN-y production. Neither type I IFNs nor IL-I 2 are critically involved in the DC-N K cell cross - talk. It can be inferred that DCs are at the interplay between innate and adaptive immune responses.
· The importance of each of the two interferon (IFN) systems and B and T cells in impeding herpesvirus replication is not completely understood. Therefore, wild type 129 Sv/Ev and congenic mice with deleted IFN receptors were infected with attenuated Pseudorabies virus (aPRV). In mice without mature B and T cells, the IFN-system type I (IFN-a/b) or the IFN- system type II (IFN-y) alone could prevent systemic disseminaUon of aPRV after infection, possibly by rapid induction of acute phase proteins. By contrast, mice without B and T cells and no IFN system were unable to clear systemic aPRV. Mice with mature B and T cells but without IFN system eliminated replicating aPRV and produced Ab of all lgG isotypes similar to wild type mice.
Literature
Wu L,D'Amico A,Winkel KD,Suter M,Lo D,Shortman K. Immunity 1998; 9: 839A7
Fernandez NC, Lozier A, Flament C, Ricciardi-Castagnoli P, Bellet D Suter M, Perricaudet M,
Maraskovsky E, Zitvogel L. Nature Medicine 1999; in press
Grob P, Schijns VECJ, van den Broek MF, Cox PJS, Ackermann M, Suter M J.Virol. 1999; in press
|
