has related document
has knowledgeable contact person
Datasets  >  preclinical study dataset  >  DC-induction of T cell resp...

DC-induction of T cell responses

preclinical study dataset

We have data available on the role of chemokine receptors in regulating migration of mature DC and subsets of effector and memory T cells in secondary lymphoid organs. CCR7 is a chemokine receptor that is expressed by mature DCs and central memory T cells (TCM) and regulate migration of these cells in secondary lymphoid organs in the steady state. T lymphocytes lacking the lymph node homing receptors L-selectin and CCR7 do not migrate to lymph nodes in the steady state. In contrast it was found that lymph nodes that drain sites of mature DC or adjuvant inoculation recruited L-selectin- CCR7- effector and memory CD8+ T cells. This cell recruitment required CXCR3 expression on T cells and occurred through high endothelial cells (HEV) in concert with HEV luminal expression of the CXCR3 ligand CXCL9. In reactive lymph nodes, recruited T cells established stable interactions with and killed antigen-bearing DC, limiting the ability of these DCs to activate naive CD4+ and CD8+ T cells. The inducible recruitment of blood-borne effector and memory T cells to lymph nodes may represent a mechanism for terminating primary and limiting secondary immune responses. In addition to CD8+ TEM, CD4+ TEM also migrated in a CD62P-dependent fashion into reactive lymph nodes that were induced to stably express CD62P on high endothelial venules. CD4+ TEM, but not naïve or TCM cells, constitutively expressed CD40L at levels sufficient to induce DC maturation in vitro and in vivo in the absence of antigenic stimulation. Presentation of a MOG peptide by TEM-licensed DC was sufficient to induce experimental allergic encephalomyelitis. Importantly, DC maturation and autoimmunity were inhibited by antibodies to CD62P that prevented CD4+ TEM migration into lymph nodes. These results provide a mechanistic link between lymphocyte traffic in lymph nodes and induction of autoimmune diseases.

We are currently investigating how CDP to cDC and pDC development is guided by external stimuli in vitro and in vivo. To this end, we evaluate the differentiation pathways upon inflammatory stimuli as TLR agonists. Furthermore, we have generated cytokine deficient animals (GM-CSF-/-Flt3L-/-) with the intention to test the combined effects of these cytokines on DC development in vivo. Also, we are in collaboration with Dr. Tim Sparwasser's laboratory at the TU Munich currently generating Flt3 and Flt3L reporter mice with the intention to elucidate in vivo DC developmental regions in steady state and inflammation in situ.







created over 8 years ago (2 March 2009)    last modified over 6 years ago (12 December 2011)   [ RDF Rdf ]   [ RelFinder Relfinder ]