Antiviral immunity, Biotherapy and Vaccines  - INSERM U668  

  HEADDr GOUGEON Marie-Lise /
Dr POIRIER Béatrice / Dr PONCET Pascal / Dr SAIDI Héla

  Annual Report

Our research unit is involved in basic immunology, studying innate and adaptive immune responses specific for viruses and tumor cells in human hosts. Moreover, we are deeply involved in clinical immunology participating to phase I/II vaccine and immunotherapy trials. Some of them evaluate new vaccine candidates, developed by research teams in Pasteur Institute against malaria, shigellosis, anthrax or cancer.

Apoptosis as a viral strategy to escape immune attack

We discovered that HIV is inducing in vivo inappropriate programmed cell death (apoptosis) in non-infected lymphocytes from the host, thus impairing both T cell homeostasis and HIV-specific T cell immunity, leading to AIDS (Reviewed in ML Gougeon, Nature Rev Immunol, 2003, 3:392-405). This last year we demonstrated the important role of the co-receptor CXCR4 in HIV-dependent triggering of cell death. In patients, we found that multiple mechanisms of CD4/CXCR4-induced cell death were operative, some of them being independent of the known death systems. These observations challenge the possible detrimental effect of anti-chemokine receptor therapies in AIDS.

iNKR expression by virus-specific CTL impairs the control of viral replication

CD8+ T-cells with cytotoxic (CTL) activity play a pivotal role in controlling viral infections. However, in most patients chronically infected with HIV, the CTL response is inefficient in the control of viral replication. We discovered that HIV-specific CTLs express MHC class-I specific inhibitory receptors, normally expressed on NK cells (iNKRs), which inhibit their activation and functions in response to HIV peptides. The expression of iNKRs is driven by HIV viral load. We are currently analyzing the role of these receptors on the cross-talk between NK-DC, two important components of innate immunity.

Molecular characterization of TCR repertoire diversity. Implementation in clinical studies

Immunoscope technology is a RT-PCR based approach that allows both to estimate the human αß TCR diversity with V(J)C primers, and to target specific clonotypes in a complex population (Figure)

With this approach, we provided new insights into the differentiation pathways of memory T cells, we showed the involvement of regulatory T cells in melanomas, and the positive impact of adoptive cell therapy on TCR repertoire diversity of Melan-A specific T cells.

An immunomonitoring laboratory for the evaluation of immune responses in clinical trials.

We have settled a number of high-tech methods to measure parameters of specific immunity induced in vivo by vaccine candidates in volunteers. A shigellosis vaccine is currently tested by our team.



Publications 2006 of the unit on Pasteur's references database

Activity Reports 2006 - Institut Pasteur
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