Although naive C.B-17 and BALB/cBy mice die of meningoencephalitis within 5 weeks of intravenous infection with an opportunistic strain of Cryptococcus neoformans, immunized mice express an acquired, CD4 ؉ T-cell-dependent immunity and survive an intravenous infection. Infusion of lymphocytes from immune mice into severe combined immunodeficiency (SCID) mice renders these mice more resistant to cryptococcal brain infection than uninfused controls. We have investigated the role of gamma interferon (IFN-␥) and tumor necrosis factor (TNF) in acquired resistance to C. neoformans. Neutralization of either IFN-␥ or TNF impaired resistance of immune BALB/cBy or C.B-17 mice to cryptococci. At 10 days postinfection, there were approximately 10 times as many yeast cells in the brains of mice treated with either anticytokine antibody as in the brains of mice treated with control antibody. Simultaneous neutralization of IFN-␥ and TNF further exacerbated infection. Neutralization of IFN-␥ or TNF also impaired resistance in immune lymphocyte-infused SCID mice, resulting in significantly higher yeast burdens in brains of cytokine-neutralized mice than in brains of controls. Concurrent neutralization of IFN-␥ and TNF rendered SCID recipients of immune cells equivalent to uninfused SCID mice with respect both to brain yeast burdens at 10 days and to survival. Anti-TNF treatment alone also curtailed survival. Histological examination of the brains of cytokine-neutralized mice revealed deficiencies in ability to focus inflammatory cells at brain lesions. These data demonstrate that both IFN-␥ and TNF are important mediators of acquired resistance to cryptococcal meningoencephalitis.

This paper describes the development and validation of the PULSE Vision & Change Rubrics, version 1.0, a reliable tool for measuring departmental change. It was found that liberal arts institutions are farther along in implementing the recommendations of Vision and Change and that institutions overall earned the highest scores on the Curriculum rubric and the lowest scores on the Assessment rubric.

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