Improving graduate education to support a branching career pipeline: recommendations based on a survey of doctoral students in the basic biomedical sciences.

Today's doctoral programs continue to prepare students for a traditional academic career path despite the inadequate supply of research-focused faculty positions. We advocate for a broader doctoral curriculum that prepares trainees for a wide range of science-related career paths. In support of this argument, we describe data from our survey of doctoral students in the basic biomedical sciences at University of California, San Francisco (UCSF). Midway through graduate training, UCSF students are already considering a broad range of career options, with one-third intending to pursue a non-research career path. To better support this branching career pipeline, we recommend that national standards for training and mentoring include emphasis on career planning and professional skills development to ensure the success of PhD-level scientists as they contribute to a broadly defined global scientific enterprise.

Class Ia MHC-deficient BALB/c mice generate CD8+ T cell-mediated protective immunity against Listeria monocytogenes infection.

CD8(+) T cells are required for protective immunity against intracellular pathogens such as Listeria monocytogenes. In this study, we used class Ia MHC-deficient mice, which have a severe reduction in circulating CD8(+) T cells, to determine the protective capacity of class Ib MHC-restricted T cells during L. monocytogenes infection. The K(b-/-)D(b-/-) mutation was backcrossed onto a C.B10 (BALB/c congenic at H-2 locus with C57BL/10) background, because BALB/c mice are more susceptible to Listeria infection than other commonly studied mouse strains such as C57BL/6. C.B10 K(b-/-)D(b-/-) mice immunized with a sublethal dose of L. monocytogenes were fully protected against a subsequent lethal infection. Adoptive transfer of Listeria-immune splenocyte subsets into naive K(b-/-)D(b-/-) mice indicated that CD8(+) T cells were the major component of this protective immune response. A CD8(+) T cell line isolated from the spleen of a Listeria-infected class Ia MHC-deficient mouse was shown to specifically recognize Listeria-infected cells in vitro, as determined by IFN-gamma secretion and cytotoxicity assays. Adoptive transfer of this T cell line alone resulted in significant protection against L. monocytogenes challenge. These results suggest that even a limited number of class Ib MHC-restricted T cells are sufficient to generate the rapid recall response required for protection against secondary infection with L. monocytogenes.