Rapport d'activité 2008

The main scientific objectives of the Lymphocyte Population Biology Unit are:

 

  • To study the mechanisms of homeostasis, which control the number oaf B and T lymphocytes.
  • To study the dynamics of the lymphocyte populations: rates of cell production and cell death, mechanisms of lymphocyte survival.
  • To study the role of cellular competition in lymphocyte selection and immune responses.
  • To study the mechanisms of immunological memory persistence.

 

To investigate these different issues we have followed several lines of research during 2008:

 

1- Bystander CD4+ T cell help to CD8+ T cells during lymphopenia driven proliferation (LDP).
Since a fully functioning immune system requires a variety of lymphocyte sub-sets,  lymphpocyte homeostasis should control both absolute numbers and relative sizes of each sub-population; otherwise, deregulation and disease may occur. We studied CD8:CD4 T cell interactions during LDP. We found that the co-transfer of CD8+ T cells sub-sets with naïve CD4+ cells results in the 10-fold increase of the number of CD8+ T cells recovered irrespectively of the CD8 T cell sub-set transferred. This “bystander helper” effect results in the preferential accumulation of cells with a TEM phenotype. The mechanisms that mediate the CD4 bystander helper require close vicinity between the interacting CD4 and 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 hosts unable to produce B cells. Using this experimental model we found that there are mechanisms of feedback regulation controlling the total number of activated B cells and B cell terminal differentiation. We have found that the IgG produced by the first B cell population controls the production of IgM by the second B cell population. Our findings suggest that the number of activated IgM-secreting B cells may be controlled by quorum-sensing mechanisms: when Ig levels reach a certain threshold, these “signals” are captured by receptors at the B cell surface that inhibit new B cell activation.

 

3- Endogenous TCR recombination in TCR transgenic Rag-2 deficient mice. 
The transfer of monoclonal TCR Tg T cells from Rag-2-/- mice, into allogenic Rag-/-gc-/- hosts results in the accumulation in the host mice of donor T cells expressing non-Tg TCRs. Molecular analysis of the expressed TCRs confirmed that these donor T cells expressed a broad diversity of recombined endogenous TCRs. Nucleotide sequence analysis indicates that we are in presence of a “classical” Rag-dependent recombination in spite of the Rag-deficiency of the donors. We found that the T cells expressing non-transgenic TCRs pre-exist in a very limited number both in the thymus and at the periphery of the donor Rag-2-/- mice.

 

Key words : lymphocyte homeostasis / immunological memory / regulatory T cells

Mis à jour le 28/01/2014

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Actualités

Publication d'un livre  "Tractus Immuno-Logicus : a brief history of the Immune System" par Pr Antonio Freitas (eds. Landes Bioscience)

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Biologie des Populations Lymphocytaires
Institut Pasteur        
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