Claire HIVROZ PhD in Immunology
Course and current status
Birth: 04/09/1961
Current position: Director of Research at the INSERM (DR2). Team leader "Etude du dialogue entre lymphocytes T et cellules dendritiques” (INSERM U932, Immunité et Cancer) at the Curie Institute.
Education
2002 : Habilitation à diriger des recherches de Paris 5.
1989 : PhD from the University Paris 7, “Study of the activation of human B lymphocytes from Chronic Lymphocytic Leukemia”. Hôpital Saint Louis, Paris (dir. J-C Brouet). Mention très honorable avec félicitations du jury.
1985 : D.E.A. from the University Paris 7, Hôpital Saint Louis, Paris (dir. J-C Brouet), mention très bien.
Research Positions
Since 1998: INSERM U932 (Dir.S. Amigorena), Institut Curie, Paris. Team leader.
Since 2002 : Director of Research at the INSERM
1991-1998: Postdoctoral position paid by ANRS , then team leader in INSERM U429, (dir. Pr A. Fischer), Hôpital Necker, Paris. “Study of the control of T cell activation by CD4 and characterization of primary immunodeficiencies associated with defects of TCR signaling”
1989-1991: postdoctoral position at Imperial Cancer Research Fund., (dir. Doreen Cantrell), London. “Regulation of transcription by TCR signaling in human T lymphocytes”
1985-1989: PhD student, “Study of the activation of human B lymphocytes from Chronic Lymphocytic Leukemia”. Hôpital Saint Louis, Paris (dir. Pr J-C Brouet).
Expertise, Teaching
Responsible of an immunology course in L3 at ENS (since 2004).
Member of the Ligue contre le Cancer scientific commitee (2005-2008)
Member of the INCA scientific committee (2007-2008)
Member of the scientific commitee of SIDACTION (since 2009)
Supervisor of 6 PhDs.
Total number of publications from 1986 to 2010: 78, h-index: 26)
Scientific summary
Team « Cross-talk between dendritic cells and T lymphocytes », leader Claire Hivroz
The general objective of our studies is to understand the mechanisms underlying human T lymphocyte activation. In order to study these mechanisms, we associate several approaches:
1) Study of a structure that is necessary to T lymphocyte and antigen presenting cells (APC) activation: the immunological synapse.
2) Study with biophysical tools of T cell activation.
3) Study of the activation of T lymphocytes whose functions are perturbed by pathologies (primary immunodeficiencies or HIV infections).
1) The immunological synapse :
Setting up an adaptive immune response requires the recognition by the TCR of MHC-peptides on the surface of antigen presenting cells (APC). This recognition requires a direct interaction between the two cell types and is accompanied by activation of the T lymphocyte and the APC, which are both necessary to mounting an efficient immune response. The interaction zone between T lymphocyte and APC is organized in time and space and has been called: the immune synapse. The formation of this zone favors the interaction and exchange of information between the two cell types. It is characterized by remodeling of the actin and microtubule cytoskeletons that leads to the polarization of the T lymphocyte toward the APC. We are studying the control of this polarity by signaling molecules, its role in cytokine secretion and activation of T lymphocytes and APC. We have shown that CD154, a major activator of dendritic cells (DC), is recruited and concentrated at the IS formed between human primary T cells and autologous DCs and that this recruitment requires T cell polarity at the IS. Moreover, we show that T cell polarization at the IS controls T cell-dependent CD154-CD40 signaling in DCs as well as CD154-dependent IL-12 secretion by DCs. This study shows that T cell polarity at the IS plays a key role in CD154/CD40-dependent cross-talk between CD4(+) T cells and DCs (Tourret et al., 2010).
2) Study with biophysical tools of T cell activation.
T lymphocyte activation requires a cell to cell contact, which involves interaction forces between the cell partners. Whereas many studies have investigated the receptors and signaling cascades involved in these interactions, little is known on the mechanical processes that accompany these cell-cell contacts. In order to explore these phenomena we collaborate with biophysicists (N. Henry, J. Husson, Institut Curie) and set up together a simplified model that allowed us to measure the biophysical aspects of the interaction between T lymphocytes and antigen presenting cells (Carpentier et al., 2009). We have shown that TCR engagement on T cells induces pushing and pulling forces on the antigen presenting cells, which depend on actin cytoskeleton remodeling. These forces developed by T cells adapt to the rigidity of the antigen presenting cells suggesting that the biomechanical environment of T cells might influence their activation.
3) Study of the activation of T lymphocytes whose functions are perturbed by pathologies:
Understanding how cell function often requires to perturbing their functions. We are studying T lymphocytes whose functions are altered by genetic hereditary mutations (primary immunodeficiencies) or by infection by a virus that modifies T cell functions: the HIV. This approach allows us to analyze some activation mechanisms but also to better understand serious pathologies. We participate in diagnostic of primary immunodeficiencies. This year, we have characterized mutations in the zap70 encoding gene in three patients. In collaboration with Alain Fischer’s group, Hôpital Necker, we have thus described the first hypomorphic ZAP70 mutation in an immunodeficient patient (Picard et al., 2009a).
We also participated in the studies of patients presenting immunodeficiencies characterized by defects of Ca2+ mobilization in response to TCR activation. We have been able to demonstrate the role of the STIM1 (Picard et al., 2009b) and ORAI1 molecules (McCarl et al., 2009) in these defects.
Finally, in collaboration with Olivier Schwartz’s group (Institut Pasteur), we have also showed that the HIV Nef protein, which is a pathogenic factor of HIV virus, modifies T lymphocyte cytoskeleton and inhibits T cell migration (Nobile et al., 2010).
