CD103 Deficiency Prevents Graft-versus-Host Disease but Spares Graft-versus-Tumor Effects Mediated by Alloreactive CD8 T Cells

Graft-versus-host disease (GVHD) remains the main barrier to broader application of allogeneic hematopoietic stem cell transplantation (alloSCT) as a curative therapy for host malignancy. GVHD is mediated by allogeneic T cells directed against histocompatibility antigens expressed by host tissues. Based on previous studies, we postulated that the integrin CD103 is required for CD8-mediated GVHD, but not for graft-versus-tumor effects (GVT).We herein provide evidence in support of this hypothesis. To circumvent the potentially confounding influence of donor CD4 T cells, we developed an alloSCT model in which GVHD mortality is mediated by purified CD8 T cells. In this model, host-reactive CD8 T cells receive CD4 T cell help at the time of initial activation but not in the effector phase in which mature CD8 T effectors migrate into host tissues. We show that donor CD8 T cells from wild-type BALB/c mice primed to host alloantigens induce GVHD pathology and eliminate tumors of host origin in the absence of host CD4 T cells. Importantly, CD103 deficiency dramatically attenuated GVHD mortality, but had no detectable impact on the capacity to eliminate a tumor line of host origin. We provide evidence that CD103 is required for accumulation of donor CD8 T cells in the host intestinal epithelium but not in the tumor or host lymphoid compartments. Consistent with these data, CD103 was preferentially expressed by CD8 T cells infiltrating the host intestinal epithelium but not by those infiltrating the tumor, lamina propria, or lymphoid compartments. We further demonstrate that CD103 expression is not required for classic CD8 effector activities including cytokine production and cytotoxicity.These data indicate that CD103 deficiency inhibits GVHD pathology while sparing anti-tumor effects mediated by CD8 T cells, identifying CD103 blockade as an improved strategy for GVHD prophylaxis

Economically Important Sharks and Rays of Indonesia

Resource /Energy Economics and Policy,

Towards an adaptive model for simulating growth of marine mesozooplankton: A macromolecular perspective

Ultimately, the structure and functioning of marine ecosystems is defined by the transfer of autotrophic production to higher trophic levels and selective consumption of these autotrophs by predators. Hence, feeding regulation via modification of grazing and food incorporation by predators is critical for understanding and predicting the dynamics of ecosystems. In marine ecosystem and biogeochemical models, feeding regulation by consumers is assumed to be mainly dictated by food quality (Q), which is determined using food quality modules (FQMs) that mimic a consumers’ ability to anticipate fitness consequences for feeding on specific prey items. Current FQMs are based on frameworks that a priori identify specific food components, usually nitrogen (N), and/or phosphorus, as limiting. This negates the importance of consumer physiology, and ignores biochemical constrains on the limiting role of chemical elements in animal production. To help address these problems, we propose a new adaptive approach that bases Q on consumers’ capacity for food uptake and metabolic physiology. Uniquely, it (i) has separate pathways for the utilisation of carbon (C) associated with proteins, lipids and carbohydrates, (ii) considers stage-specific structural biochemical requirement of animals, and (iii) does not treat consumers’ structural demand for carbon as a “unitary requirement” but discriminates among the required biochemical forms of carbon. The approach is applicable to all heterotrophs. In the example given here the model has been configured to represent the calanoid copepod Acartia tonsa. Consistent with experimental observation, but unlike previous models, our model predicts the relationship between Q and food C:N to be unimodal with a maximum Q only at the threshold C:N for biomass production. Results suggest that prey C:N ratios may be irrelevant for food quality due to macromolecular biochemical constrains on the utilisation of chemical elements. This result emphasizes the importance of biochemical substances in animal nutrition and production as well as the necessity of developing food quality models able to adapt to the biochemical needs of the consumer