Dynamics of Immune Responses


  HEADDr BOUSSO Philippe / bousso@pasteur.fr
  MEMBERSDr AZAR Georges / Dr BREART Beatrice / Dr CELLI Susanna / BEUNEU Hélène


  Annual Report

The orchestration of an adaptive immune response relies on a succession of dynamic molecular and cellular events taking place in specialized micro-environments. The outcome of T cell responses is influenced by contact-dependent information exchanges between various cell subsets, including CD4 and CD8 T lymphocytes, antigen-presenting cells and regulatory T cells. In the laboratory, we are studying how T cell responses are regulated by cell migration and by cell-cell interactions in lymph nodes. A combination of intravital two photon imaging with detailed functional studies is used to dissect T cell activation and function in vivo.

Visualizing the initial stages of T cell activation

Previous studies have proposed that transient contacts between T cells and dendritic cells (DCs) precede the formation of long-lived interactions. We have recently developed a new experimental approach to quantify and visualize the onset of T cell activation in vivo. Using intravital two photon imaging (Fig. 1), we found that the first encounter between antigen-bearing DCs and cognate CD4 T cells most often resulted in the formation of a long-lived interaction. This system is further used to dissect the requirement for T cell stop.

T cell competition during immune responses

We found that while prolonged interactions between activated T cells and Ag-bearing DCs were infrequent at high T cell precursor frequency, they were readily observed for a period of at least 2 days when lower numbers of T cells were used. In fact, when present in high numbers, Ag-specific T cells were competing for the limited number of sites on DCs with sufficient peptide-MHC (pMHC) complexes for the establishment of a long-lived interaction. Thus, the period during which CD4 T cells continue to establish stable interactions is dictated both by Ag levels and T cell numbers, providing a feed-back mechanism for the termination of CD4 T cell responses.

Cellular dynamics during CD4 T cell help

In many instances, CD4 helper T cells promote the quality of CD8 T cell responses, a phenomenon referred to as CD4 help. The cellular orchestration underlying CD4 help is not fully understood. We have identified a new facet to the phenomenon of CD4 help in which DCs, upon cognate interactions with CD4 T cells, increase their ability to attract/retain Ag-specific CD8 T cells. Our results support a model in which CD4 help operates rapidly, in part by favoring CD8 T cells recruitment around those DCs that are the most competent for priming.

bousso.jpg

Figure 1. La formation d’interactions stable entre LT (rouge) et DC (vert) peut se produire en l’absence de contacts transitoires. Les résultats ont été obtenus par imagerie biphotonique du ganglion poplité d’une souris anésthésiée.

Figure 1. Rapid formation of long-lived interactions between CD4 T cells (red) and antigen-bearing dendritic cells (green) in vivo. Results were obtained using intravital two photon imaging of the popliteal lymph node of a living mouse.



  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
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