The Pasteur Museum is housed in the apartment where Louis Pasteur spent his final seven years and offers a rare behind-the-scenes look at the living and working environment of the world-renowned scientist. Visitors can gain a unique insight into his everyday life alongside his wife and can admire his rich and diverse scientific work.
The Institut Pasteur’s scientific strategy focuses on developing original and innovative topics and promoting interdisciplinary and multidisciplinary cooperation and approaches. The Institut Pasteur teams have access to the technological resources needed to speed up and further improve the quality of their outstanding research.
Ever since the introduction of the world’s first "Technical Microbiology" course in 1889, teaching has been a priority for the Institut Pasteur. The Institut Pasteur has an international reputation for quality teaching that attracts students from all over the world who come to further their training or top up their degree programs.
The mission of the Industrial Partnership team is to detect, promote, assist and protect the inventive activities from research (inventions, know-how and biological materials) conducted at the Institut Pasteur (and in some Institutes of its international network), and transfer there to industrial and/or institutional partners, in order to serve the patient needs and for the benefit of the society, as well as to contribute to sustainability of the Institut Pasteur’s resources.
With international courses, PhD and postdoctoral traineeship, each institute of the Institut Pasteur International Network (RIIP) contributes to the transmission of knowledge with the training of young researchers all around the world. In this context, doctoral and postdoctoral programmes, study and traineeship fellowships are available to scientists. Alongside training, dynamism and attractiveness of RIIP will result in the creation of 4-year group for the young researchers.
The main scientific objective of the Lymphocyte Population Biology Unit are:
To study the mechanisms of homeostasis, which control the number of B and T lymphocytes.
To study the role of cellular competition in lymphocyte selection and immune responses.
To study the mechanisms of immunological memory persistence.
In 2010 we followed several lines of research:
1- Bystander CD4+ T cell help to CD8+ T cells during lymphopenia driven proliferation (LDP).
We studied the fate of selected populations of CD8+ and CD4+ T cells in T cell deficient CD3ε-/- mice. We found that the reconstitution of the CD8+ T cell pool is independent of the nature of the CD8+ T cells transferred, suggesting that the resulting pools are environmentally controlled. However, co-transfer of CD8 T cells with CD4+ T cells modifies CD8+ T cell recovery - results in the dramatic increase of the CD8+ T cell numbers recovered. This “helper” effect generates preferentially an increased number of CD8 T cells expressing a TEM phenotype and cytotoxic effector molecules and is does not alter the number of cells with a TCM phenotype. We showed that during LDP bystander CD4 T cell help did not involve CD40 expression by the expanding CD8 T cells, but required CD40 expression by host non-lymphoid cells. Using cells from mice invalidated for the CCR5 molecule we showed that the helper effects also require close vicinity between the interacting CD4 and CD8 T cells. Moreover the bystander helper effects were dependent on IL-2 produced by the expanding CD4+ T cells and required expression of IL-2Rb chain but not of the IL-2Ra chain by the responding CD8+ T cells. Thus, plasticity on the TEM-phenotype CD8+ T cell niche contrasts with stringent homeostatic mechanisms in TCM-phenotype CD8+ T cell numbers and points to different homeostatic control mechanisms for TCM and TEM-phenotype CD8+ T cells.
2. Selection and control of IgM-secreting cells.
We studied the fate of mature lymph node (LN) B cells injected into immune-deficient Rag° hosts. We found that a fraction of the transferred population of LN B cells expanded and persisted for prolonged periods of time. A significant fraction of the surviving B cells express an activated MZ B cell phenotype and were actively engaged in IgM-secretion. Serum IgM concentrations identical to those of control mice were readily reached in the presence of a reduced number of B cells. We investigated different aspects of the biology of the natural IgM-secreting cells. We found that mechanisms of feedback regulation control the number of activated B cells. We have found that the IgG produced by the first B cell population controls the production of IgM by the second B cell populations. Mouse IgG passively administered into Rag-deficient hosts strongly inhibits the activation and IgM production by adoptively transferred B cells. More recently, we found that B cells from FcγRIIB-/- donors are not suppressed. These findings suggest that the number of activated IgM-secreting cells may be controlled by quorum-sensing mechanisms and that when the serum Ig levels reach a determined threshold, these “signals” are captured by receptors at the B cell surface that inhibit B cell activation.
3- The homeostasis of the IL-2 producing T cells.
We have shown that the interactions between the CD4+CD25+ regulatory T cells and naïve CD25-CD4+ T cells are of major relevance for the establishment of peripheral CD4 T cell homeostasis. We demonstrated that the IL-2Ra is an absolute requirement for the generation of the regulatory cells. The expression of the high-affinity IL-2Ra endows these cells with the capacity to explore the IL-2 resource, which ensures their peripheral survival, while keeping their number tied to the number of CD4+ T cells that produce IL-2. The indexing of CD4+CD25+Foxp3+ Treg cells to the number of activated IL-2-producing CD4+ T cells may constitute a feedback mechanism that controls T cell expansion during immune responses, thus preventing autoimmune or lymphoproliferative diseases. These results indicated that the number of IL-2-producing cells is relevant for regulatory T cells homeostasis as they may control their maintenance in the peripheral pools. These findings indicate that a quorum-sensing feedback loop, where the IL-2 produced by T cell sub-population is detected by a sub-population of CD4 Treg cells expressing the high-affinity IL-2Ra-chain that controls the number of total CD4 T cells. That is to say: overall CD4 T cell populations adapt their behavior according to the detection of the quantities of IL-2 produced. We are currently investigating The properties and homeostasis of IL-2 producing (IL-2p) T cells.
Keywords: lymphocyte homeostasis / immunological memory / regulatory T cells