How cAMP contributes to improve antigen detection by T cells
A cAMP increase triggered in a T cell by its interaction with a dendritic cell is schown in false colours
In the body, naive T lymphocytes oscillate between two states : suspended cells in lymph or blood vessels, and adherent cells within secondary lymphoid organs like lymph nodes. In these organs, T lymphocytes explore their neighbourhood and interact with dendritic cells (DC), that are the most important antigen-presenting cells. As soon as a T cell touches a DC, this initial contact triggers a marked increase in the sensitivity of the T cell for detecting rare antigenic complexes (and in particular for triggering a calcium response). We have named AITCP (« Adhesion-Induced T Cell Priming »), this phenomenon first described in our laboratory (Randriamampita et al, European Journal of Immunology (2003) 33:1215-1223).
By combining biochemical methods with different techniques of dynamic fluorescence imaging (and in particular with the measurement of cAMP at the single cell level), we have elucidated the molecular mechanism underlying AITCP. This work, published in January 2009 (Conche et al, (2009) Immunity 30 :33-43) has been highlighted in a Preview by Kortum & Samelson (Immunity 30 :3- 5). We have shown that the adhesion of lymphocytes on fibronectin or on DCs elicited a transient increase in cAMP in the T lymphocyte, that was key for AITCP. This is a very surprising result, as it is well established that a sustained increase in cAMP efficiently inhibits an immune response. Thus, the same signal, depending on its kinetics, may have completely different functional consequences. A transient cAMP increase allows an indirect activation of the ERK kinase due to the inhibition of a phosphatase, HePTP. This novel signaling cascade explains key steps that allow a T cell to switch from a low sensitivity state (circulating cells) to a high sensitivity state (within lymph nodes).
Article:
Immunity. 2009 Jan;30(1):33-43.
Contacts:
Randriamampita C.
INSTITUT COCHIN (U.567 Inserm/UMR8104 CNRS/UMR-S8104) Bâtiment Gustave Roussy - Hôpital Cochin 27, Rue du Faubourg Saint-Jacques 75014 PARISEmail : clotilde.randriamampita@inserm.fr
Trautmann A.
INSTITUT COCHIN (U.567 Inserm/UMR8104 CNRS/UMR-S8104) Bâtiment Gustave Roussy - Hôpital Cochin 27, Rue du Faubourg Saint-Jacques 75014 PARIS
Email : alain.trautmann@inserm.fr
