The Role of Invariant Natural Killer T Cells in Dendritic Cell Licensing, Cross-Priming, and Memory CD8+ T Cell Generation

New vaccination strategies focus on achieving CD8+ T cell (CTL) immunity rather than on induction of protective antibody responses. While the requirement of CD4+ T (Th) cell help in dendritic cell (DC) activation and licensing, and in CTL memory induction has been described in several disease models, CTL responses may occur in a Th cell help independent manner. Natural Killer T cells (NKT cells) can substitute for Th cell help and license DC as well. NKT cells produce a broad spectrum of Th1 and Th2 cytokines, thereby inducing a similar set of costimulatory molecules and cytokines in DC. This form of licensing differs from Th cell help by inducing other chemokines: while Th cell licensed DC produce CCR5 ligands, NKT cell-licensed DC produce CCL17 which attracts CCR4+ CD8+ T cells for subsequent activation. It has recently been shown that iNKT cells do not only enhance immune responses against bacterial pathogens or parasites, but also play a role in viral infections. The inclusion of NKT cell ligands in Influenza virus vaccines enhanced memory CTL generation and protective immunity in a mouse model. This review will focus on the role of iNKT cells in the cross-talk with cross-priming DC and memory CD8+ T cell formation

Valsts un baznīcas attiecības Itālijā pēc Laterana līgumiem: diplomdarbs

Pielikums: Baznīcas valstij piešķirto īpašumu plāni

Penser le style comme événement à l’aune des concepts de « manière » et d’« individuation »

Partant du socle épistémologique de la sémiotique des cultures remise à l’honneur aujourd’hui en sciences du langage, cette contribution explore une double hypothèse théorique, sans esquiver les difficultés qu’elle peut soulever : celle, largement partagée par la stylistique contemporaine, d’une possible reconception du style comme résultat d’un processus d’individuation et celle, plus délicate, d’un possible développement du concept d’« individuation » à travers la mobilisation de la notion classique de « manière » reprise et réévaluée par Gérard Dessons. Cette double hypothèse, pour autant qu’on la manie avec discernement, présente un intérêt heuristique dans la mesure où elle permet d’approfondir les liens entre style et événement, à partir d’une constellation de thèmes interdépendants : prise de forme, relance du sens, spécificité, imprévisibilité, persistance dans le présent, portée collective du singulier

Comment gagner la proximité sans perdre la distance ou comment construire du commun avec de l’écart ? Sémiotique des cultures et approche critique de la notion d’« actualisation »

Si la notion d’« actualisation » est à première vue séduisante, n’a-t-elle pas le défaut d’encourager une certaine paresse égotiste, une subjectivité anhistorique qui instrumentalise les œuvres, cautionnant une lecture spontanée non critique et laissant supposer que le travail d’objectivation rimerait nécessairement avec déplaisir ou ennui ? On proposera un cadre théorique et des applications pratiques qui permettent de maintenir un point de vue historicisant tout en construisant une approche dynamique des textes, c’est-à-dire de « gagner la proximité sans perdre la distance » (Merleau-Ponty).If the notion of “actualization” is appealing at first sight, does it not have the fault of encouraging a certain narcissistic laziness, an a-historical subjectivity which exploits the works, supporting a spontaneous, non-critical reading and leaving one to suppose that the work of objectification would necessarily be synonymous with displeasure or boredom? We will propose a theoretical framework and practical applications which permit one to hold a soundly historical point of view while also building a dynamic approach to texts, that is to say “to gain proximity without losing distance” (Merleau-Ponty)

Chemokines: A New Dendritic Cell Signal for T Cell Activation

Dendritic cells (DCs) are the main inducers and regulators of cytotoxic T lymphocyte (CTL) responses against viruses and tumors. One checkpoint to avoid misguided CTL activation, which might damage healthy cells of the body, is the necessity for multiple activation signals, involving both antigenic as well as additional signals that reflect the presence of pathogens. DCs provide both signals when activated by ligands of pattern recognition receptors and “licensed” by helper lymphocytes. Recently, it has been established that such T cell licensing can be facilitated by CD4+ T helper cells (“classical licensing”) or by natural killer T cells (“alternative licensing”). Licensing regulates the DC/CTL cross-talk at multiple layers. Direct recruitment of CTLs through chemokines released by licensed DCs has recently emerged as a common theme and has a crucial impact on the efficiency of CTL responses. Here, we discuss recent advances in our understanding of DC licensing for cross-priming and implications for the temporal and spatial regulation underlying this process. Future vaccination strategies will benefit from a deeper insight into the mechanisms that govern CTL activation

Class I–restricted Cross-Presentation of Exogenous Self-Antigens Leads to Deletion of Autoreactive CD8+ T Cells

In this report, we show that cross-presentation of self-antigens can lead to the peripheral deletion of autoreactive CD8+ T cells. We had previously shown that transfer of ovalbumin (OVA)-specific CD8+ T cells (OT-I cells) into rat insulin promoter–membrane-bound form of OVA transgenic mice, which express the model autoantigen OVA in the proximal tubular cells of the kidneys, the β cells of the pancreas, the thymus, and the testis of male mice, led to the activation of OT-I cells in the draining lymph nodes. This was due to class I–restricted cross-presentation of exogenous OVA on a bone marrow–derived antigen presenting cell (APC) population. Here, we show that adoptively transferred or thymically derived OT-I cells activated by cross-presentation are deleted from the peripheral pool of recirculating lymphocytes. Such deletion only required antigen recognition on a bone marrow–derived population, suggesting that cells of the professional APC class may be tolerogenic under these circumstances. Our results provide a mechanism by which the immune system can induce CD8+ T cell tolerance to autoantigens that are expressed outside the recirculation pathway of naive T cells

Major Histocompatibility Complex Class I–restricted Cross-presentation Is Biased towards High Dose Antigens and Those Released during Cellular Destruction

Naive T cells recirculate mainly within the secondary lymphoid compartment, but once activated they can enter peripheral tissues and perform effector functions. To activate naive T cells, foreign antigens must traffic from the site of infection to the draining lymph nodes, where they can be presented by professional antigen presenting cells. For major histocompatibility complex class I–restricted presentation to CD8+ T cells, this can occur via the cross-presentation pathway. Here, we investigated the conditions allowing antigen access to this pathway. We show that the level of antigen expressed by peripheral tissues must be relatively high to facilitate cross-presentation to naive CD8+ T cells. Below this level, peripheral antigens did not stimulate by cross-presentation and were ignored by naive CD8+ T cells, although they could sensitize tissue cells for destruction by activated cytotoxic T lymphocytes (CTLs). Interestingly, CTL-mediated tissue destruction facilitated cross-presentation of low dose antigens for activation of naive CD8+ T cells. This represents the first in vivo evidence that cellular destruction can enhance access of exogenous antigens to the cross-presentation pathway. These data indicate that the cross-presentation pathway focuses on high dose antigens and those released during tissue destruction