Mechanisms of the natural reactivity of lymphocytes from noninfected individuals to membrane-associated Leishmania infantum antigens.

Membrane-associated Leishmania Ags (MLA) or soluble Leishmania Ags were used in vitro to stimulate cord blood or PBMC from healthy donors noninfected by Leishmania parasites. MLA, but not soluble Leishmania Ags, constantly induce strong proliferation of cord blood mononuclear cells and PBMC from noninfected individuals. Responding cells are CD3+, CD4+, TCRalphabeta+, CD45RO+, and CD45RA+ and secrete IFN-gamma and IL-10, but not IL-4.

A profound alteration of blood TCRB repertoire allows prediction of cerebral malaria.

Cerebral malaria (CM) is one of the severe complications of Plasmodium infection. In murine models of CM, Talphabeta cells have been implicated in the neuropathogenesis. To obtain insights into the TCRB repertoire during CM, we used high throughput CDR3 spectratyping and set up new methods and software tools to analyze data.

Comparative study of brain CD8+ T cells induced by sporozoites and those induced by blood-stage Plasmodium berghei ANKA involved in the development of cerebral malaria.

To obtain insight into the mechanisms that contribute to the pathogenesis of Plasmodium infections, we developed an improved rodent model that mimics human malaria closely by inducing cerebral malaria (CM) through sporozoite infection. We used this model to carry out a detailed study on isolated T cells recruited from the brains of mice during the development of CM. We compared several aspects of the immune response related to the experimental model of Plasmodium berghei ANKA infection induced by sporozoites in C57BL/6 mice and those related to a blood-stage infection.

New methods and software tools for high throughput CDR3 spectratyping. Application to T lymphocyte repertoire modifications during experimental malaria.

Immune repertoires of T or B cells are very often studied by Complementary Determining Region 3 (CDR3) spectratyping. However, data obtained with this method is usually subject to a biased eye analysis. We developed recently the ISEApeaks software package to retrieve and handle peak data from automated sequencers, from which CDR3 spectratype data is obtained.

A new statistical method for quantitative analyses: application to the precise quantification of T cell receptor repertoires.

In experimental immunology, a situation quite commonly arises in which there are a large number of potential events but the probability of any individual event is small and one wishes to measure the number of events which actually occur. We present a new general statistical method, denoted Continuous Poisson Method (COPOM), for estimating the number of events underlying a quantitative measurement. This situation is well illustrated in the case of quantitative analyses of the immune receptor repertoire in a diverse population of cells.