Gabrielle Belz

....

....

..This review focuses on the recent progress in our understanding of the molecular wiring of this differentiation process...

..Here, we review the current understanding of the role of Id2 in lymphopoiesis and in the development of the adaptive immune response required for maintaining immune homeostasis and immune protection...

..Thus, self-Ag can be carried to the draining lymph nodes by skin-derived DCs and there presented by these same cells for tolerization of the circulating T cell pool...

..These observations have important implications for the design of prophylactic and therapeutic DC vaccines and contribute to the understanding of the mechanisms causing immunosuppression during systemic blood infections...

....

..Interestingly, Blimp-1 expression is controlled by the same cgammaC cytokines that regulate T cell homeostasis suggesting a direct link between the extrinsic and intrinsic arms of the process...

..Collectively, these findings show that Puma contributes to the death of antigen-specific T cells during shutdown of an immune response...

..These data identify IL-18 as a crucial factor for pDC-mediated NK cell regulation...

..The ability of the memory T cells to remove antigen-presenting cells provides a negative-feedback loop to directly limit the duration of antigen presentation in vivo...

..Latent antigen-specific CD4(+) T cells therefore either failed to recognize key virus-infected cell populations in vivo or lacked the effector functions required to control them...

..This conclusion has important implications for the design of vaccination strategies based on antigen targeting to DC...

..Moreover, inhibition of cross-presentation was overcome by injection of dendritic cells bearing antigen, which provides a new strategy for generating immunity during immunosuppressive blood infections...

..As Langerhans cells are radioresistant, unlike other DC populations, these studies also demonstrate that the radiosensitive DC responsible for secondary expansion of HSV-specific memory are not Langerhans cells...

..We show that regardless of the type of intracellular infection, CD8alpha(+) DCs are the principal DC subset that initiate CD8(+) T cell immunity...

..The conference was funded by the Australian Department of Innovation, Industry, Science and Research...

..Thus, these data uncover a role for Bid in coordinating apoptotic signaling pathways to ensure appropriate shutdown of T cell immune responses in the setting of persistent Ag exposure...

..These results show that a pathogen with the capacity to interfere with early Ag presentation can establish suboptimal conditions for rapid induction of the adaptive immune response and thus favor establishment of viral persistence...

..Therefore, in the absence of both CD37 and Tssc6, immune function is further altered when compared with CD37(-/-) or Tssc6(-/-) mice, demonstrating a complementary role for these two molecules in cellular immunity...

..In this issue of Immunity, Pipkin et al. (2010) and Kalia et al. (2010) link differential interleukin-2 signaling and inflammation with the transcriptional events leading to the development of effector and memory cells...

..Understanding these interactions has begun to allow us to understand how integration of different populations in the DC network responds to multiple scenarios of infection...

....

..This study identifies Blimp-1 as a master regulator of the terminal differentiation of CD8(+) effector T cells and uncovers a conservation of the pathways that regulate the terminal differentiation of T and B cells...

..These findings indicate that despite the capacity of CTLs to produce inflammatory cytokines and to cause tissue damage, their responses are not sustaining, but instead favor induction of self-tolerance...

..Thus, CD40L upregulation on DCs promoted optimal priming of CD8(+) T cells without CD4(+) T cells, providing a mechanism by which pathogens may elicit helper-independent CTL immunity...

..Understanding the 'rules of the race' for slow growing pathogens has important implications for vaccine design and immune control of many chronic infections...

..Understanding how such contrasting kinetics of Ag presentation impacts on the growth and size of developing protective T cell populations has important implications for the design of vaccines and immunotherapies...

..As the antigen-presenting abilities of cDCs and pDCs are fundamentally distinct, these two cell types may activate largely nonoverlapping repertoires of CD4(+) T cells...

..Finally, using three different experimental approaches, we provide evidence that CTL specific for parasite-expressed antigens contribute to ECM...

..In this issue of Immunity, Aoshi et al. (2008) highlight the fact that the migratory route DCs take to drive T cell activation is independent of the architecture of lymphoid tissues...

..This Opinion describes this finding in the context of antigen transfer between migrating and lymphoid-resident DCs in cases of T-cell priming and tolerance induction...

..This indicates that pharmacological inhibition of Bim function might be useful for boosting immune responses in immunodeficient patients...

..In situations in which DCs are poorly licensed by pathogen-derived signals, our findings suggest that CTL immunity may be heavily dependent on cognate DC licensing...

..Any population of "resting" CD8(+) memory T cells is thus phenotypically heterogeneous, widely dispersed, and subject to broad homeostatic and local environmental effects irrespective of epitope specificity or magnitude...

..Perhaps the main lesson learned to date is that all the components of immunity are likely to be important for the control of these complex viruses...

..The overall conclusion is that turnover rates substantially in excess of 5 to 10% over 6 days for CD8+ "memory" T-cell populations are likely to be reflective of continued antigenic exposure...

..The results for the K(b)PB1(703) epitope and the PB2(198) mimotope also provide a cautionary tale for those using the cytokine staining approach to identity antigenic peptides...

....

..Previous CD8(+)-T-cell immunodominance heirarchies defined largely by cytotoxic T-lymphocyte assays may need to be revised...

..Even very high levels of virus-specific CD8(+) T cells thus provide only transient protection against the uniformly lethal consequences of gammaHV-68 infection under conditions of CD4(+) T cell deficiency...

....

..The CD8+ T cell population recognizing productively infected epithelial cells thus differed substantially from that responding during the IM illness...

..It seems that CD8(+) T cells alone are insufficient to maintain long-term control of this persistent gamma-herpesvirus...

..In the tonsils of the soft palate of pigs, HEV may mediate both lymphocyte migration to and from the lymphoid tissue. Further investigation is required to determine the importance of these 2 migration pathways...

..Septal, basal and efferent lymphatic vessels contain prominent valves and many lymphocytes. Lymphatic sinuses appear to be a significant pathway for lymphocytes migrating from the tonsillar lymphoid tissue...

..The aim of this study was to describe the architecture of the tonsillar crypst and the morphology of their epithelial surface...

..As the vessels from the tonsils course over the surface of the pharynx, the muscular movements of swallowing may help propel lymph towards the primary nodes and the bloodstream...

..This contrasts with the commonly accepted description which implies that all blood vessels to all lymph nodes pass through a well defined hilus...

..Basal vessels course within the central lamina and converge to form efferent lymphatic vessels which emerge at the caudal region of the palatine tonsil and convey lymph to the medial retropharyngeal lymph node...

..Efferent vessels emerge along the hilus and coalesce to form the tracheal trunk. The tracheal trunk has several layers of smooth muscle cells, well developed elastic laminae and connective tissue, surrounding the lymphatic endothelium...

..These studies demonstrate that some degree of cytotoxicity via either perforin or Fas is essential for CD8(+) T cells to control this DNA virus...

..A fenestrated basement membrane allows cell transport between the intraepithelial passageways of the reticular epithelium and the subepithelial lymphoid tissues...

..These data highlight the general role played by CD8alpha(+) DCs in CTL priming to viral infection and raises the possibility that this DC subset is specialized for viral immunity...

..CD4 T cells may only be capable of activating one dendritic cell during the period that CD8 T cells are primed. In this case, corecognition of this same dendritic cell would be essential...

..Presentation by a nonairway-derived DC population argues that cytotoxic T lymphocyte priming may involve interplay between different DC subsets, not all of which originate within the site of infection...

....

..In this review, we identify some of the features and properties of DCs, and how these properties can be exploited in the design of smart vaccines...

..Here we review recent experiments that provide insights into how DC subsets control the outcome of T cell activation and in so doing select between immunity and tolerance induction...

..In these models, CD36 knockout DCs were equivalent to wild-type DCs in their capacity to cross-present either foreign or self Ags, indicating that CD36 is not essential for cross-presentation of cellular Ags in vivo...

..In this review, we examine the molecular basis for cross-presentation, discuss the role of DC subsets, and examine the contribution of this process to immunity, with some emphasis on DNA vaccination...

..These findings suggest that when precursor frequencies are high, priming of CD8 T cell responses may not require CD4 T cell help...

..These data identify Blimp-1 as an essential regulator of T cell homeostasis and suggest that Blimp-1 regulates both B cell and T cell differentiation...

..CD4(+) T cell priming by DC subsets that is dependent upon the route of administration raises the possibility that vaccination approaches could be tailored to prime helper T cell immunity...

..Therefore, the lymphoid organs contain a large cohort of immature DCs, most likely for the maintenance of peripheral tolerance, which can respond to infections reaching those organs and mature in situ...

..Given that such class I-restricted presentation is essential for CTL priming, this implies that these conventional CD8alpha(+) dendritic cells are the key subset involved in CTL immunity to this virus...

..Further, we endeavour to examine how the molecular signals imparted by DCs coordinate to generate protective CD8(+) T-cell immunity...

..Thus, the traditional view of Langerhans cells in epidermal immunity needs to be revisited to accommodate a requirement for other dendritic cells in this response...

..These findings are consistent with mathematical models that predict virus-host dynamics in this, and other, models of infection...

..Our results support that, during persistent viral infection, continual presentation of lytic Ags by DC leads to T cell activation critical for maintaining CD8(+) T cells capable of limiting persistent viral infection...

..These results identify critical overlapping roles for Fas and Bim in T cell death in immune response shutdown and prevention of immunopathology and thereby resolve a long-standing controversy...

..Thus CTL immunity was independent of CD4+ T cells in a chronic herpesvirus infection, but was still inadequate to control virus replication...