Long-term research projects can provide important conservation benefits, not only through research specifically focused on conservation problems, but also from various incidental benefits, such as ...increased intensity of monitoring and building support for the protection of an area. At Gombe National Park, Tanzania, long-term research has provided at least four distinct benefits to wildlife conservation. (1) Jane Goodall's groundbreaking discoveries of chimpanzee (Pan troglodytes) tool use, hunting, and complex social relationships in what was then a game reserve drew attention to the area and created support for upgrading Gombe to national park status in 1968. (2) The highly publicized findings have earned Gombe and Tanzania the attention of a worldwide public that includes tourists and donors that provide financial support for Gombe, other parks in Tanzania, and chimpanzee conservation in general. (3) Crucial information on social structure and habitat use has been gathered that is essential for effective conservation of chimpanzees at Gombe and elsewhere. (4) A clear picture of Gombe's chimpanzee population over the past 40 years has been determined, and this has helped identify the greatest threats to the viability of this population, namely disease and habitat loss outside the park. These threats are severe and because of the small size of the population it is extremely vulnerable. Research at Gombe has led to the establishment of conservation education and development projects around Gombe, which are needed to build local support for the park and its chimpanzees, but saving these famous chimpanzees will take a larger integrated effort on the part of park managers, researchers, and the local community with financial help from international donors.
FOXP3+ regulatory T (Treg) cells are indispensable for immune homeostasis, but their study in humans is complicated by heterogeneity within Treg, the difficulty in purifying Tregs using surface ...marker expression (e.g. CD25) and the transient expression of FOXP3 by activated effector cells. Here, we report that expression of CD39 and CD45RO distinguishes three sub-populations within human CD4(+)CD25(hi) T cells. Initial phenotypic and functional analysis demonstrated that CD4(+)CD25(hi)CD39(+)CD45RO(+) cells had properties consistent with effector Treg, CD4(+)CD25(hi)CD39(-)CD45RO(-) cells were naïve Treg and CD4(+)CD25(hi)CD39(-)CD45RO(+) cells were predominantly non-Treg with effector T-cell function. Differences in these two newly identified Treg subsets were corroborated by studies of gene expression and TCR analysis. To apply this approach, we studied these two newly identified Treg subsets in ankylosing spondylitis, and showed impairment in both effector and naïve Treg. This work highlights the importance of discriminating Treg subsets to enable proper comparisons of immune regulatory capacity in healthy individuals and those with inflammatory disease.
Foxp3 is proposed to play a critical role in the development and function of regulatory T cells. Functional and transgenic studies in mice propose Foxp3 as a "regulatory T cell lineage specification ...factor" but conflicting data exist in humans. Expression of multiple Foxp3 splice variants in humans represents an additional layer of complexity for this transcription factor and acts as a possible mechanism of regulating protein diversity. We report the identification of a novel splice variant of Foxp3, called Foxp3 Delta 7, in ex vivo CD4+CD25+ T cells and CD8+ regulatory T cell clones. Foxp3 Delta 7 lacks the 81 bp region that encodes exon 7 of Foxp3, which is a part of the leucine zipper domain of the protein. The three splice variants of Foxp3 namely Foxp3FL, Foxp3 Delta 2 and Foxp3 Delta 7 are co-expressed in ex vivo human CD4+CD25+ T cells and CD8+ Treg clones. Stimulation of freshly isolated CD4+CD25+ T cells with anti-CD3 and anti-CD28 antibodies leads to a 140-fold upregulation of Foxp3 Delta 7 within 24 h of stimulation, which is inline image10-fold greater than that observed in stimulated CD4+CD25- T cells. In addition, resting CD8+ Treg cells have decreased expression of Foxp3FL and Foxp3 Delta 2; however they have a 10-fold higher expression of Foxp3 Delta 7, in comparison to ex vivo CD4+CD25+ T cells. In order to assess the functional effects of these Foxp3 isoforms, we carried out lentivirus expression studies. All three isoforms were capable of inducing increased levels of CD25 expression in primary human CD4+ T cells, along with a tendency to decreased levels of CD127. Further investigation into pathways that alter the relative proportions of Foxp3 isoforms, and hence their interaction with other transcriptional co-regulators, will help to define the role of Foxp3 isoforms in immune regulation.
To analyze the frequency and phenotype of peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cell (SFMC) T helper (Th)17 cells in reactive arthritis (ReA).
T cell surface ...phenotype and cytokine production were measured following stimulation, using 8-color flow cytometry.
The percentages of interleukin 17 (IL-17)-positive CD4+ T cells were increased in SFMC of patients with ReA compared with PBMC. All IL-17+ cells were CD4+CD45RO+; in SFMC most expressed CCR6, but only 50% expressed CCR4. IL-17+ cells sometimes coexpressed IL-22 and/or interferon-γ, but not IL-10.
These data support the hypothesis that Th17 cells are involved in ReA pathogenesis.
Like human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus of chimpanzees (SIVcpz) can cause CD4+ T cell loss and premature death. Here, we used molecular surveillance tools and ...mathematical modeling to estimate the impact of SIVcpz infection on chimpanzee population dynamics. Habituated (Mitumba and Kasekela) and non-habituated (Kalande) chimpanzees were studied in Gombe National Park, Tanzania. Ape population sizes were determined from demographic records (Mitumba and Kasekela) or individual sightings and genotyping (Kalande), while SIVcpz prevalence rates were monitored using non-invasive methods. Between 2002-2009, the Mitumba and Kasekela communities experienced mean annual growth rates of 1.9% and 2.4%, respectively, while Kalande chimpanzees suffered a significant decline, with a mean growth rate of -6.5% to -7.4%, depending on population estimates. A rapid decline in Kalande was first noted in the 1990s and originally attributed to poaching and reduced food sources. However, between 2002-2009, we found a mean SIVcpz prevalence in Kalande of 46.1%, which was almost four times higher than the prevalence in Mitumba (12.7%) and Kasekela (12.1%). To explore whether SIVcpz contributed to the Kalande decline, we used empirically determined SIVcpz transmission probabilities as well as chimpanzee mortality, mating and migration data to model the effect of viral pathogenicity on chimpanzee population growth. Deterministic calculations indicated that a prevalence of greater than 3.4% would result in negative growth and eventual population extinction, even using conservative mortality estimates. However, stochastic models revealed that in representative populations, SIVcpz, and not its host species, frequently went extinct. High SIVcpz transmission probability and excess mortality reduced population persistence, while intercommunity migration often rescued infected communities, even when immigrating females had a chance of being SIVcpz infected. Together, these results suggest that the decline of the Kalande community was caused, at least in part, by high levels of SIVcpz infection. However, population extinction is not an inevitable consequence of SIVcpz infection, but depends on additional variables, such as migration, that promote survival. These findings are consistent with the uneven distribution of SIVcpz throughout central Africa and explain how chimpanzees in Gombe and elsewhere can be at equipoise with this pathogen.
Foxp3 is proposed to play a critical role in the development and function of regulatory T cells. Functional and transgenic studies in mice propose Foxp3 as a "regulatory T cell lineage specification ...factor" but conflicting data exist in humans. Expression of multiple Foxp3 splice variants in humans represents an additional layer of complexity for this transcription factor and acts as a possible mechanism of regulating protein diversity. We report the identification of a novel splice variant of Foxp3, called Foxp3Δ7, in ex vivo CD4+CD25+ T cells and CD8+ regulatory T cell clones. Foxp3Δ7 lacks the 81bp region that encodes exon 7 of Foxp3, which is a part of the leucine zipper domain of the protein. The three splice variants of Foxp3 namely Foxp3FL, Foxp3Δ2 and Foxp3Δ7 are co-expressed in ex vivo human CD4+CD25+ T cells and CD8+ Treg clones. Stimulation of freshly isolated CD4+CD25+ T cells with anti-CD3 and anti-CD28 antibodies leads to a 140-fold upregulation of Foxp3Δ7 within 24h of stimulation, which is ∼10-fold greater than that observed in stimulated CD4+CD25- T cells. In addition, resting CD8+ Treg cells have decreased expression of Foxp3FL and Foxp3Δ2; however they have a 10-fold higher expression of Foxp3Δ7, in comparison to ex vivo CD4+CD25+ T cells. In order to assess the functional effects of these Foxp3 isoforms, we carried out lentivirus expression studies. All three isoforms were capable of inducing increased levels of CD25 expression in primary human CD4+ T cells, along with a tendency to decreased levels of CD127. Further investigation into pathways that alter the relative proportions of Foxp3 isoforms, and hence their interaction with other transcriptional co-regulators, will help to define the role of Foxp3 isoforms in immune regulation.
Female chimpanzees often forage alone and do not display obvious linear dominance hierarchies; consequently, it has been suggested that dominance is not of great importance to them. However, with the ...use of data from a 35-year field study of chimpanzees, high-ranking females were shown to have significantly higher infant survival, faster maturing daughters, and more rapid production of young. Given the foraging behavior of chimpanzees, high rank probably influences reproductive success by helping females establish and maintain access to good foraging areas rather than by sparing them stress from aggression.
Despite substantial advances in our understanding of CD4+CD25+ regulatory T cells, a possible equivalent regulatory subset within the CD8+ T cell population has received less attention. We now ...describe novel human CD8+/TCRαβ+ T cells that have a regulatory phenotype and function. We expanded and cloned these cells using autologous LPS‐activated dendritic cells. The clones were not cytolytic, but responded in an autoreactive HLA class I‐restricted fashion, by proliferation and production of IL‐4, IL‐5, IL‐13 and TGFβ1, but not IFN‐γ. They constitutively expressed CD69 and CD25 as well as molecules associated with CD4+CD25+ regulatory T cells, including cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4) and Foxp3. They suppressed IFN‐γ production and proliferation by CD4+ T cells in vitro in a cell contact‐dependent manner, which could be blocked using a CTLA‐4‐specific mAb. They were more readily isolated from patients with ankylosing spondylitis and may therefore be up‐regulated in response to inflammation. We suggest that they are the CD8+ counterparts of CD4+CD25+ regulatory T cells. They resemble recently described CD8+ regulatory cells in the rat that were able to abrogate graft‐versus‐host disease. Likewise, human HLA‐restricted CD8+ regulatory T cells that can be cloned and expanded in vitro may have therapeutic applications.
Performance and Evolution in the Age of Darwin reveals the ways in which the major themes of evolution were taken up in the performing arts during Darwin's adult lifetime and in the generation after ...his death. The period 1830-1900 was the formative period for evolutionary ideas. While scientists and theorists investigated the law and order of nature, show business was more concerned with what was out of the natural order. Missing links and throwbacks, freak taxonomies and exotic races were favourite subject matter for the burgeoning variety theatre movement. Focusing on popular theatre forms in London, New York and Paris, Jane Goodall shows how they were interwoven with the developing debate about human evolution. With this book, Goodall contributes an important new angle to the debates surrounding the history of evolution. She reveals that, far from creating widespread culture shock, Darwinian theory tapped into some of the long-standing themes of popular performance and was a source for diverse and sometimes hilarious explorations.
Jane R. Goodall is currently Director of Research in the College of Arts, Education and Social Sciences at the University of Western Sydney where she specialises in the development of cross-disciplinary research. She is the author of Artaud and the Gnostic Drama (1994).
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