- Since June 2005:
Group leader "HIV pathogenesis and Immune aging"
at the Infections and Immunity INSERM Unit UMR S 945 (Paris, France)
Directors: Professor Patrice Debré and Dominique Mazier
- March 2004 to May 2005
Project manager: Study of Melanoma specific CD8+ T cells during immunotherapy
at the Centre Pluridisciplinaire d’Oncologie (CePO) (Lausanne, Switzerland)
Directors: Professor Pedro Romero and Serge Leyvraz
- July 1998 to December 2003
Research engineer and research associate (from January 2002):
Study of virus specific CD8+ T cells in HIV-1 infection
at the Weatherall Institute of Molecular Medicine (Oxford, UK)
Directors: Professor Sarah Rowland-Jones and Andrew McMichael
- March to June 1998
Research engineer: Refolding of HPV‑16 specific ScFv in vitro
at the E.S.B.S laboratories (Strasbourg, France)
Director: Professor Etienne Weiss
- January to December 1997
Research assistant: Study of the effects of CC-chemokines on T lymphocytes
at British Biotech Pharmaceuticals Ltd. (Oxford, UK)
Director: Dr Lloyd Czaplewski
T cells play a key role in our defenses against foreign pathogens, including HIV. CD4+ and CD8+ T-cells participate to the establishment of immunological memory, the founding principle of vaccinology.
I. An important research focus of my research is on defining T-cell correlates of efficacy, that is to say specific attributes of T cells which are associated with a better control of HIV replication in infected donors. The T-cell compartment is very heterogeneous, and consists in a variety of T-cell subpopulations with different functional capacities and ability to control pathogens like HIV. I aim at identifying the subsets of T-cells that are able to suppress viral replication in HIV infected patients (e.g. those who do not progress towards AIDS) and decipher the T-cell attributes and mechanisms which permit this control are important for vaccine development. This will indeed guide the design of candidate vaccines, in order that these vaccines can induce T-cells with such advantageous attributes in men. The recent work of my team indicates that T-cells with high sensitivity for HIV antigens (that is to say the avidity of the T-cell for its target, the HIV infected cell) are associated with a superior control of HIV replication. High avidity T-cells are more functional, and can recognize and eliminate more efficiently target cells, compared to low avidity counterparts. Perspectives of this work include the development of strategies to influence the T-cell sensitivity or avidity using adjuvants to be used in human vaccines.
II. Another central topic of research in my group is on the reasons behind the onset of immunodeficiency in HIV infection. A consensus has emerged regarding the association between chronic immune activation and poor outcome in HIV infection; nonetheless its basis remains unclear. In this context, we are interested in the concept of immunosenecence and its role in HIV pathogenesis. Our work focuses on studying immune characteristics related to T-cell development and renewal (from the generation of T-cells to their senescence), activation and inflammation in HIV infected individuals, in parallel with HIV non infected elderly in order to reveal immunological correlates of immunodeficiency. Our recent findings indicate that immune activation and inflammation lead to accelerated immunosenescence, or decay of immunity, hence HIV disease progression. Persistent activation results in global exhaustion of hematopoitic resources, resulting in the lack of T-cell renewal and altered homeostasis. In the context of studying the consequences of immune activation and inflammation, we are also investigating the impact of CMV infection in different settings like HIV infection, thymectomy during early childhood, or lung transplantation. The establishment of robust CMV specific T cell responses appears to be associated with exhaustion of T cell resources, as well as collateral inflammatory damage. Our perspectives include the development of means to prevent or slow down the detrimental effects of immune activation and inflammation of viruses like HIV or CMV. This work is highly relevant to our understanding of HIV pathogenesis, and more generally of immunogerontology.