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ABSTRACT: Protection against pathogens is mediated by both humoral responses (neutralizing antibodies) and cellular immunity, both CD4+ and CD8+ cells. In the case of influenza viruses, circulating strains contain both variable and conserved T and B cell epitopes that are challenged after vaccination and/or infection. During infection, the role of T cells is to prevent viral dissemination in the organism by killing the infected cells and helping B cell antibody production to neutralize the virus. The threat of influenza virus increases the preparedness of protective immunity to pandemic and seasonal infection by vaccination. Several questions remain that need to be further addressed for the future development of innovative and rapidly efficient vaccines strategies. Firstly, what are the correlates of long-term protection (antibodies and/or T cells) against variant strains of influenza? How does the individual factors (age, natural immunity, vaccination and/or infection history) influence the generation and maintenance of memory cells? What are the factors allowing the maintenance of immune memory (regular contact with the pathogen or re-vaccination)? Secondly, what is the nature and quality (function / phenotype / location) of memory B and T cells? Finally, is it necessary to induce and maintain immunological memory against conserved proteins and/or to re-vaccinate against viral variants? What would be the consequences of repeated vaccination? These questions remain a subject of debate that will be further discussed. Since immunological memory is the cornerstone of vaccination, it is essential that we have a better understanding of its generation and maintenance over time as well as its contribution to recall responses during pandemics or after vaccination.
Pathologie Biologie 03/2010; 58(2):e79-86. · 1.53 Impact Factor
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ABSTRACT: Smallpox virus eradication was one of the greatest successes of the 20th century. Moreover, the quest to combat its use in biological warfare, has fueled efforts to understand residual immune memory and to develop new animal models by the scientific community. Although the literature is full of animal studies of vaccinia virus infection, continuing efforts have helped to increase our knowledge regarding humoral and cellular memory to non-persistent pathogens and to study factors that might influence further vaccination strategies in humans. In addition, the potent immunostimulatory action of poxvirus vectors has led to development and evaluation of new-generation vaccine candidates, which will be discussed in this review.
Cellular and Molecular Life Sciences CMLS 11/2006; 63(19-20):2249-59. · 6.57 Impact Factor
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ABSTRACT: Smallpox virus eradication was one of the greatest successes of the 20th century. Moreover, the quest to combat its use in
biological warfare, has fueled efforts to understand residual immune memory and to develop new animal models by the scientific
community. Although the literature is full of animal studies of vaccinia virus infection, continuing efforts have helped to
increase our knowledge regarding humoral and cellular memory to non-persistent pathogens and to study factors that might influence
further vaccination strategies in humans. In addition, the potent immunostimulatory action of poxvirus vectors has led to
development and evaluation of new-generation vaccine candidates, which will be discussed in this review.
Cellular and Molecular Life Sciences CMLS 09/2006; 63(19):2249-2259. · 6.57 Impact Factor
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ABSTRACT: The use of the smallpox virus as a biological weapon is very old. Confronted with a high probability of a current bioterrorist menace, counteracting strategies have been developed. One of the principle aims relies on the vaccination of teams dedicated to the management of persons infected and the stocking of vaccine for the whole population of a country. Following worldwide eradication of the disease, preventive vaccination was topped in 1978 in France for the primo-vaccination, and in 1984 for repeat vaccinations. The various strains used in the first generation vaccinations are weakened living vaccine, the natural host and origin of which is unknown. Second and third generations vaccines are under study; the principle objective is to obtain efficacy with a minimum of side effects. There are two types of adverse events, generally observed with the first generation vaccines: the first, extremely rare, can be life-threatening; the others, more frequent (10 to 15% of patients) are benign. In emergency situations, in the presence of smallpox, there should be no absolute contraindications to vaccination. In the bioterrorist context, massive vaccination campaigns of the population are unadvisable (because of the considerable risk of death and severe adverse events) in the absence of any real permit, in each case, definition of the vaccinal strategy to be adopted.
La Presse Médicale 02/2005; 34(2 Pt 2):177-184. · 0.67 Impact Factor
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ABSTRACT: Clonal selection theories postulate that lymphocyte fate is regulated by antigen receptor specificity. However, lymphocyte apoptosis is induced through nonantigen-specific receptors such as Fas (CD95/APO-1) or TNFR. We define a selective TCR that controls apoptosis by Fas or TNFR stimulation. Variant ligands can deliver this "competence to die" signal without the full TCR signals necessary for cytokine synthesis. These partial agonists regulate T cell deletion in vivo even when Fas or TNF is provided by T cells of unrelated specificity, but they do not cause the liver necrosis that is associated with T cell elimination by the full agonist. Thus, selective signaling ligands regulate T cell deletion and immune damage in vivo and may be important for peripheral T cell tolerance.
Immunity 10/1998; 9(3):305-13. · 21.64 Impact Factor
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ABSTRACT: Activation, anergy, and apoptosis are all possible outcomes of T cell receptor (TCR) engagement. The first leads to proliferation and effector function, whereas the others can lead to partial or complete immunological tolerance. Structural variants of immunizing peptide-major histocompatibility complex molecule ligands that induce selective lymphokine secretion or anergy in mature T cells in association with altered intracellular signaling events have been described. Here we describe altered ligands for mature mouse CD4(+) T helper 1 cells that lead to T cell apoptosis by the selective expression of Fas ligand (FasL) and tumor necrosis factor (TNF) without concomitant IL-2, IL-3, or interferon gamma production. All ligands that stimulated cell death were found to induce FasL and TNF mRNA expression and TCR aggregation ("capping") at the cell surface, but did not elicit a common pattern of tyrosine phosphorylation of the TCR-associated signal transduction chains. Thus, TCR ligands that uniquely trigger T cell apoptosis without inducing cytokines that are normally associated with activation can be identified.
Journal of Experimental Medicine 03/1998; 187(3):349-55. · 13.85 Impact Factor
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ABSTRACT: Engagement of the T cell receptor (TCR) of mature T lymphocytes can lead either to activation/proliferation responses or programmed cell death. To understand the molecular regulation of these two fundamentally different outcomes of TCR signaling, we investigated the participation of various components of the TCR-CD3 complex. We found that the TCR-zeta chain, while not absolutely required, was especially effective at promoting mature T cell apoptosis compared with the CD3 epsilon, gamma, or delta chains. We also carried out mutagenesis to address the role of the immunoreceptor tyrosine-based activation motifs (ITAMs) that are the principal signaling components found three times in the TCR-zeta chain and once in each of the CD3 epsilon, gamma, or delta chains. We found that the ability of the TCR-zeta chain to promote apoptosis results both from a quantitative effect of the presence of multiple ITAMs as well as qualitatively different contributions made by individual ITAMs. Apoptosis induced by single chain chimeras revealed that the first zeta ITAM stimulated greater apoptosis than the third zeta ITAM, and the second zeta ITAM was unable to trigger apoptosis. Because microheterogeneity in the amino acid sequence of the various ITAM motifs found in the TCR-zeta and CD3 chains predicts interactions with distinct src-homology-2-domain signaling proteins, our results suggest the possibility that individual ITAM motifs might play unique roles in TCR responses by engaging specific signaling pathways.
Journal of Experimental Medicine 06/1996; 183(5):2109-17. · 13.85 Impact Factor
