Information Technology Reference
In-Depth Information
Fig. 3
. Distribution of induced and repressed genes in dendritic cells responding to viruses.
The differences between viruses that infect DCs and those that do not, either
through lack of DC tropism or because they are inactivated, have important
implications for understanding immune control of viral infections. Certain viruses
such as human immunodeficiency virus (HIV) (Izmailova, Bertley, Huang, Makori,
Miller, Young, and Aldovini 2003) and murine cytomegalovirus (Andrews,
Andoniou, Granucci, Ricciardi-Castagnoli, and Degli-Esposti 2001) are known to
infect DCs and prevent authentic maturation. How these viruses prevent the
maturation program is not known but should allow the identification of crucial
functional gene networks that are required for DC maturation. In addition, the
differences in DC transcriptional responses to live and inactivated influenza imply
that inactivated vaccines may not produce the complete transcriptional repertoire that
leads to fully authentic immunization. Understanding such differences should
improve both vaccines for infectious agents and vaccines directed against tumors.
7.3.3 Transcriptional Plasticity Toward T
H
1, T
H
2,
and Tolerogenic Immunity
Most of the DC gene expression studies have so far focused on antigens that
stimulate a T
H
1 response, raising the question as to whether transcriptional
differences will define T
H
1, T
H
2, and tolerogenic DC states. Recently Ryan et al
.
described the transcriptional changes in monocyte-derived DCs to the contact
allergen dinitrobenzenesulfonic acid (DNBS) (Ryan, Gildea, Hulette, Dearman,
Kimber, and Gerberick 2004). Many of the core DC maturation program genes were
upregulated consistent with observed DC maturation. Indications of DC gene
expression differences were identified by comparing DNBS-induced genes with
other published DC gene expression data. This suggested that Signaling Lymphocyte
Activation Molecule (SLAM), known to be highly upregulated on DCs matured by
LPS or dsRNA, was downregulated by DNBS. SLAM activation in T cells results in
the production of T
H
1 polarizing IFN-γ and in DCs in the production of IL-12 and
IL-8 (Bleharski, Niazi, Sieling, Cheng, and Modlin 2001). SLAM activity may
therefore be detrimental in a T
H
2 polarizing environment perhaps explaining its
down-regulation in DCs by DNBS.
