Impairment of host immunity, particularly CD4+ T cell deficiency, presents significant complications for vaccine immunogenicity and efficacy. CD40 ligand (CD40L or CD154), a member of the tumor necrosis factor superfamily (TNFSF), is an important co-stimulatory molecule and, through interactions with its cognate receptor CD40, plays a pivotal role in the generation of host immune responses. Exploitation of CD40L and its receptor CD40 could provide a means to enhance and potentially restore protective immune responses in CD4+ T cell deficiency. To investigate the potential adjuvanticity of CD40L, we constructed recombinant plasmid DNA and adenoviral (Ad) vaccine vectors expressing murine CD40L and the mycobacterial protein antigen 85B (Ag85B). Co-immunization of mice with CD40L and Ag85B by intranasal or intramuscular prime-boosting led to route-dependent enhancement of the magnitude of vaccine-induced circulating and lung mucosal CD4+ and CD8+ T cell responses in both normal (CD4-replete) and CD4+ T cell deficient animals, including polyfunctional T cell responses. The presence of CD40L alone was insufficient to enhance or restore CD4+ T cell responses in CD4-ablated animals; however, in partially-depleted animals, co-immunization with Ag85B and CD40L was capable of eliciting enhanced T cell responses, similar to those observed in normal animals, when compared to those given vaccine antigen alone. In summary, these findings show that CD40L has the capacity to enhance the magnitude of vaccine-induced polyfunctional T cell responses in CD4+ T cell deficient mice, and warrants further study as an adjuvant for immunization against opportunistic pathogens in individuals with CD4+ T cell deficiency.
This report documents the incidental finding of a horseshoe kidney identified during routine dissection in a gross anatomy course. The anatomic examination demonstrated malrotated bilateral kidneys, which were fused at the inferior poles. Histologic examination revealed no significant pathologic change; however, the fused portion was shown to have an intact cortex and collecting system. Furthermore, the renal vasculature was anomalous with multiple accessory and convoluted arterial vessels. An aortic aneurysm was also noted just superior to the renal fusion. Operative procedures and diagnostic imaging performed in the region of such an anatomical variation may be complicated by unanticipated vascular patterns. Therefore, special attention should be paid to vasculature in the setting of a horseshoe kidney.
Support or Funding Information
T. Walley Williams Summer Anatomy Research Fellowship;WV Research Challenge Fund [HEPC.dsr.17.06]
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