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To perform their distinct effector functions, pathogen-specific T cells have to migrate to target tissue where they recognize antigens and produce cytokines that elicit appropriate types of protective responses. Similarly, migration of pathogenic self-reactive T cells to target organs is an essential step required for tissue-specific autoimmunity. In this article, we review data from our laboratory as well as other laboratories that have established that effector function and migratory capacity are coordinately regulated in different T-cell subsets. We then describe how pathogenic T cells can enter into intact or inflamed central nervous system (CNS) to cause experimental autoimmune encephalomyelitis or multiple sclerosis. In particular, we elaborate on the role of CCR6/CCL20 axis in migration through the choroid plexus and the involvement of this pathway in immune surveillance of and autoimmunity in the CNS. [ABSTRACT FROM AUTHOR]

The immune response requires a timely interaction among different cell types within distinct microenvironments. Our studies have focused on the regulation of chemokine receptors in dendritic cells (DC) and T lymphocytes. Chemokine receptors expressed by immature DC promote their migration to inflamed tissues where antigens are captured and maturation is induced. Maturing DC upregulate CCR7, which drives their migration to the T-cell areas of the draining lymph nodes where antigen is presented to naïve T cells. DC produce a variety of chemokines that influence DC recruitment into inflamed tissues and DC-T cell interaction in the lymph nodes. Chemokine receptors are differentially acquired by developing Th1 and Th2 cells and are differentially expressed on subsets of "central memory" and "effector memory" T cells. Furthermore, following antigenic stimulation, effector T cells can rapidly switch chemokine receptor expression, acquiring new migratory capacities. These studies provide insights into the mechanisms that control T-cell priming as well as memory and effector immune responses. [ABSTRACT FROM AUTHOR]

Studies on immunologic memory in animal models and especially in the human system are instrumental to identify mechanisms and correlates of protection necessary for vaccine development. In this article, we provide an overview of the cellular basis of immunologic memory. We also describe experimental approaches based on high throughput cell cultures, which we have developed to interrogate human memory T cells, B cells, and plasma cells. We discuss how these approaches can provide new tools and information for vaccine design, in a process that we define as 'analytic vaccinology'. [ABSTRACT FROM AUTHOR]

The work of our laboratory has focused on the study of human memory B cells. Using an in vitro approach we dissected the triggering requirements of B cells and unveiled a distinct role for TLRs in the activation of naive versus memory B cells. Using an ex vivo approach we analyzed the dynamics of memory B cells and ASCs and the kinetics of serum antibodies during secondary immune responses and in steady state conditions and used these quantitative data to build up a model of serological memory. According to this model memory B cells behave as `stem cells' capable of generating plasma cells and antibodies in an antigen-dependent as well as in an antigen-independent fashion. Finally we developed an efficient method to interrogate human memory B cells and to isolate human monoclonal antibodies. This method can be exploited for the production of neutralizing antibodies for serotherapy and for “analytic vaccinology”. [ABSTRACT FROM AUTHOR]