Scientists have long predicted large-scale responses of infectious diseases to climate change, giving rise to a polarizing debate, especially concerning human pathogens for which socioeconomic drivers and control measures can limit the detection of climate-mediated changes. Climate change has already increased the occurrence of diseases in some natural and agricultural systems, but in many cases, outcomes depend on the form of climate change and details of the host-pathogen system. In this review, we highlight research progress and gaps that have emerged during the past decade and develop a predictive framework that integrates knowledge from ecophysiology and community ecology with modeling approaches. Future work must continue to anticipate and monitor pathogen biodiversity and disease trends in natural ecosystems and identify opportunities to mitigate the impacts of climate-driven disease emergence.

http://science.sciencemag.org/content/sci/341/6145/514.full.pdf

Climate Change and Infectious Diseases: From Evidence to a Predictive Framework

T cell differentiation is a progressive process characterized by phenotypic and functional changes. By transferring tumor-specific CD8+ T cells into tumor-bearing mice at various stages of differentiation, we evaluated their efficacy for adoptive immunotherapy. We found that administration of naive and early effector T cells, in combination with active immunization and IL-2, resulted in the eradication of large, established tumors. Despite enhanced in vitro antitumor properties, more-differentiated effector T cells were less effective for in vivo tumor treatment. Several events may underlie this paradoxical phenomenon: (a) downregulation of lymphoid-homing and costimulatory molecules; (b) inability to produce IL-2 and access homeostatic cytokines; and (c) entry into a proapoptotic and replicative senescent state. While the progressive acquisition of terminal effector properties is characterized by pronounced in vitro tumor killing, in vivo T cell activation, proliferation, and survival are progressively impaired. These findings suggest that the current methodology for selecting T cells for transfer is inadequate and provide new criteria for the generation and the screening of optimal lymphocyte populations for adoptive immunotherapy.

/pdf/acquisition-of-full-effector-function-in-vitro-paradoxically-54j37usyos.pdf

Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells

Adoptive cell transfer after host preconditioning by lymphodepletion represents an important advance in cancer immunotherapy. Here, we describe how a lymphopaenic environment enables tumour-reactive T cells to destroy large burdens of metastatic tumour and how the state of differentiation of the adoptively transferred T cells can affect the outcome of treatment. We also discuss how the translation of these new findings might further improve the efficacy of adoptive cell transfer through the use of vaccines, haematopoietic-stem-cell transplantation, modified preconditioning regimens, and alternative methods for the generation and selection of the T cells to be transferred.

/pdf/adoptive-immunotherapy-for-cancer-building-on-success-3jgaffa8p4.pdf

Adoptive immunotherapy for cancer: building on success.

Thorough research on HIV is progressively enabling us to understand the intricate mechanisms that link HIV-1 infection to the onset of immunodeficiency. The infection and depletion of CD4(+) T cells represent the most fundamental events in HIV-1 infection. However, in recent years, the role played by chronic immune activation and inflammation in HIV pathogenesis has become increasingly apparent: quite paradoxically, immune activation levels are directly associated with HIV-1 disease progression. In addition, HIV-1-infected patients present intriguing similarities with individuals of old age: their immune systems are characterized by a loss of regenerative capacity and an accumulation of ageing T cells. In this review, we discuss the potential reasons for the establishment of sustained immune activation and inflammation from the early stages of HIV-1 infection, as well as the long-term consequences of this process on the host immune system and health. A simplified model of HIV pathogenesis is proposed, which links together the three major facets of HIV-1 infection: the massive depletion of CD4(+) T cells, the paradoxical immune activation and the exhaustion of regenerative capacity.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/path.2276

Immune activation and inflammation in HIV-1 infection: causes and consequences.

In recent years, a tremendous effort has been devoted to the detailed characterization of the phenotype and function of distinct T cell subpopulations in humans, as well as to their pathway(s) of differentiation and role in immune responses But these studies seem to have generated more questions than definitive answers To clarify issues related to the function and differentiation of T cell subsets, one session of the MASIR 2008 conference was dedicated to this topic Several points of consensus and discord were highlighted in the work presented during this session We provide here an account of these points, including the relative heterogeneity of T cell subpopulations during infections with distinct pathogens, the relationship between phenotypic and functional T cell attributes, and the pathway(s) of T cell differentiation Finally, we discuss the problems which still limit general agreement

http://cytobase.montp.inserm.fr/ftp/Biblio/Phenotype%20and%20function%20of%20human%20T%20lymphocyte%20Subsets%20consensus%20and%20issues.pdf

Phenotype and function of human T lymphocyte subsets: Consensus and issues

Progress in the fight against the HIV/AIDS epidemic is hindered by our failure to elucidate the precise reasons for the onset of immunodeficiency in HIV-1 infection Increasing evidence suggests that elevated immune activation is associated with poor outcome in HIV-1 pathogenesis However, the basis of this association remains unclear Through ex vivo analysis of virus-specific CD8(+) T-cells and the use of an in vitro model of naive CD8(+) T-cell priming, we show that the activation level and the differentiation state of T-cells are closely related Acute HIV-1 infection induces massive activation of CD8(+) T-cells, affecting many cell populations, not only those specific for HIV-1, which results in further differentiation of these cells HIV disease progression correlates with increased proportions of highly differentiated CD8(+) T-cells, which exhibit characteristics of replicative senescence and probably indicate a decline in T-cell competence of the infected person The differentiation of CD8(+) and CD4(+) T-cells towards a state of replicative senescence is a natural process It can be driven by excessive levels of immune stimulation This may be part of the mechanism through which HIV-1-mediated immune activation exhausts the capacity of the immune system

/pdf/immune-activation-and-cd8-t-cell-differentiation-towards-33nm9ywht4.pdf

G Chesney

Papers

Immune Activation and CD8+ T-Cell Differentiation towards Senescence in HIV-1 Infection