Cytotoxicity of tumor antigen specific human T cells is unimpaired by arginine depletion.

Tumor-growth is often associated with the expansion of myeloid derived suppressor cells that lead to local or systemic arginine depletion via the enzyme arginase. It is generally assumed that this arginine deficiency induces a global shut-down of T cell activation with ensuing tumor immune escape. While the impact of arginine depletion on polyclonal T cell proliferation and cytokine secretion is well documented, its influence on chemotaxis, cytotoxicity and antigen specific activation of human T cells has not been demonstrated so far. We show here that chemotaxis and early calcium signaling of human T cells are unimpaired in the absence of arginine. We then analyzed CD8(+) T cell activation in a tumor peptide as well as a viral peptide antigen specific system: (i) CD8(+) T cells with specificity against the MART-1aa26-35*A27L tumor antigen expanded with in vitro generated dendritic cells, and (ii) clonal CMV pp65aa495-503 specific T cells and T cells retrovirally transduced with a CMV pp65aa495-503 specific T cell receptor were analyzed. Our data demonstrate that human CD8(+) T cell antigen specific cytotoxicity and perforin secretion are completely preserved in the absence of arginine, while antigen specific proliferation as well as IFN-γ and granzyme B secretion are severely compromised. These novel results highlight the complexity of antigen specific T cell activation and demonstrate that human T cells can preserve important activation-induced effector functions in the context of arginine deficiency

Future of Specialist Practice Qualifications in district nursing for band 6 leadership roles

District nurse numbers in the UK are rapidly declining. To overcome this severe staff shortage, one community trust in a rural county appointed 'case managers' (nurses without Specialist Practice Qualifications in district nursing [SPQDN]) in band 6 leadership roles that were traditionally held by district nurses. Here, we aimed to establish the value of the SPQDN to determine if there is a future for the conventionally accepted DN role, instead of case managers. The study used an exploratory mixed-methods design. Using the classic e-Delphi technique, data were collected over 5 months from 10 purposively sampled senior nurse managers employed by the community trust who formed an expert panel. In round one, the panellists provided three responses each to the question 'what is the future for district nurse specialist practitioner qualifications in [the trust] for band 6 leadership roles?' In rounds two and three, they answered a close-ended questionnaire using a 3-point Likert scale. The core findings suggest that SPQDN and the district nurse role are considered extremely valuable (both achieving 100% consensus). Additional findings are linked to four core themes, namely, (1) SPQDN, (2) clinical practice educators, (3) workforce and (4) leadership. This study recommends continued investment in SPQDN and the district nurse role with the use of succession planning for workforce management.