Anti-Ia treatment prevents lupus-like autoimmune syndrome in mice neonatally tolerized to alloantigens.

Neonatal injection of semi-allogeneic F1 spleen cells into newborn parental mice results in induction of tolerance to the corresponding class I alloantigen and chimerism. This state of tolerance is associated with the development of a transient lupus-like autoimmune syndrome. Previous experiments performed in our laboratories have shown that host CD4+ T lymphocytes and donor B cells persist in the host and are essential in triggering the autoimmune syndrome observed in neonatally tolerized mice. In this study, we show that early treatment of tolerized mice with anti-donor MHC class II mAb totally prevents the lupus-like syndrome. Moreover, delayed treatment significantly decreases, but to a lesser extent, autoimmune pathological features in tolerized mice. Taken together, these results show that lupus-like autoimmune syndrome developed by neonatally tolerized mice is efficiently prevented by anti-Ia treatment without interfering with the induction of tolerance.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

The primary cellular immune responses to B. pertussis antigens in infants

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Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens

Although it is known that the immune system can mount responses to a variety of tumors it is clear that most tumors exhibit weak or even undetectable immunogenicity. Recent findings suggest that the lack of tumor immunogenicity is partly due to a population of cells called CD4+CD25+ regulatory T cells since depletion of these cells in mice can result in tumor rejection.These cells have also been shown to inhibit the development of organ-specific autoimmune diseases suggesting that they inhibit immune responses to tissue-specific self-antigens. Such immune responses may also mediate tumor rejection. Alternatively, immune responses in mice depleted of regulatory cells may target tumor antigens that are not tissue-specific, but which are shared by tumors of diverse origins. In experiments performed to discriminate between these possibilities we found, using the murine colorectal tumor CT26, that tumor immunity stimulated in the absence of regulatory cells is not restricted to tumors of colorectal origin, but is effective against tumors of different histological types such as B cell lymphomas and a renal cell carcinoma. By comparing this to CT26-induced immunity through the use of adjuvant we show that the generation of cross-reactive tumor immunity is a specific manifestation of CD25+ regulatory cell depletion. The generation of CD4+T cells capable of mediating tumor rejection is another important feature of tumor immunity induced in the absence of CD25+ cells

Bordetella pertussis infection in 2-month-old infants promotes type 1 T cell responses.

Neonatal immaturity of the immune system is currently believed to generally limit the induction of immune responses to vaccine Ags and to skew them toward type 2 responses. We demonstrated here that Bordetella pertussis infection in very young infants (median, 2 mo old) as well as the first administration of whole-cell pertussis vaccine induces B. pertussis Ag-specific IFN-gamma secretion by the PBMC of these infants. IFN-gamma was secreted by both CD4(+) and CD8(+) T lymphocytes, and the levels of Ag-induced IFN-gamma secretion did not correlate with the age of the infants. Appearance of the specific Th-1 cell-mediated immunity was accompanied by a general shift of the cytokine secretion profile of these infants toward a stronger Th1 profile, as evidenced by the response to a polyclonal stimulation. We conclude that the immune system of 2-mo-old infants is developmentally mature enough to develop Th1 responses in vivo upon infection by B. pertussis or vaccination with whole-cell pertussis vaccines.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe