While macroglossia is a newly accepted component of brachycephalic obstructive airway syndrome (BOAS) in dogs, macroglossia with increased tongue fat is a well-known cause for obstructive sleep apnea (OSA) in people, and targeted reduction procedures such as midline glossectomy are used to treat people with OSA. While midline glossectomy has been described in dogs, tissue contributions to macroglossia have not been characterized. The purpose of this retrospective, descriptive, case-control study was to describe and compare volumetric dimensions of the tongue and tongue fat in brachycephalic (BC) and mesaticephalic (MC) dogs using CT images. Data collected included head and neck CT images from 17 BC and 18 control MC dogs. Multiplanar reformatted and 3D reconstructed images were created using image segmentation and specialized visualization software to calculate volumetric dimensions of the total tongue, tongue fat, and tongue muscle. Rostral and caudal topographical distributions of fat were compared. Total tongue and tongue muscle volume (P < 0.0001) and tongue fat volume (P = 0.01) normalized to body weight (BW) were greater in BC dogs. More fat was localized in the caudal tongue in both groups (P < 0.04). In regression analysis, BC conformation and increased weight were significant predictors of increased tongue fat volume. As in people, increased tongue fat may contribute to macroglossia and sleepdisordered breathing in BC dogs. Use of CT volumetry to identify tongue fat deposits may permit targeted surgical reduction of tongue volume in BC dogs and contribute substantially to treatment of BOAS.

Costimulation regulates multiple cellular processes including proliferation, expansion and survival of T cells, and molecular targets of costimulation might be useful to augment T cell activities. Two defined targets of costimulatory signals in CD4 T cells are the anti-apoptotic Bcl-2 family molecule Bcl-xL, and survivin, an Inhibitor of Apoptosis family member that might regulate cell division and survival. However, the relative importance and relationship between these molecules in CD8 T cells is not clear. To understand whether they have overlapping or synergistic functions, we used retroviral transduction to introduce Bcl-xL and survivin separately, or together linked by a 2A picornavirus self-cleaving peptide, into antigen-responding CD8 cells. In vitro, we found that CD8 effector T cells expressing both Bcl-xL and survivin strongly expanded at an early stage and had a long-term survival advantage. In vivo, with response to tumor-expressed Ag following adoptive T cell transfer, antigen-reactive CD8 T cells expressing both Bcl-xL and survivin displayed a greatly enhanced tumor protective activity compared CD8 cells expressing either molecule introduced separately. These results indicate that Bcl-xL and survivin can critically contribute in a synergistic, non-redundant, manner to augment the accumulation and persistence of CD8 T cells following encounter with antigen. The data provide new insights into why costimulatory signals might need to be sustained over time or provided periodically via ligation of multiple receptors.