Differential regulation of simultaneous antitumor and alloreactive CD8(+) T-cell responses in the same host by rapamycin.

Rapamycin is an immunosuppressive agent routinely used in organ transplantation but also paradoxically exerts antiviral and antitumor activities. Pathogen-specific memory CD8(+) T-cell (T(CD8) ) responses were recently found to be augmented by rapamycin. However, whether rapamycin influences the magnitude and quality of anticancer T(CD8) responses is unknown. Importantly, how rapamycin may regulate simultaneous virus/tumor-specific and alloreactive T(CD8) in the same host remains unexplored. To answer these questions, we primed wild-type mice with allogeneic cells concomitantly expressing simian virus 40 large tumor antigen (T Ag), a viral oncoprotein with well-defined epitopes. Rapamycin selectively enhanced the cross-priming of T(CD8) specific for T Ag's most immunodominant epitope called site IV but not T(CD8) alloreactivity. Rapamycin-treated mice also had a high percentage of splenic CD127(high) KLRG1(low) T(CD8) and an increased frequency of site IV-specific T cells long after the peak of their primary response. When site IV was presented as a cytosolic minigene encoded by a recombinant vaccinia virus, rapamycin failed to boost the site IV-specific response. Therefore, the nature and presentation mode of antigen determine the susceptibility to the adjuvant effect of rapamycin. Our findings reveal the unexpected benefit of rapamycin treatment in recipients of allografts co-expressing tumor/viral Ags.

Food search demand effort effects on behavior and cortisol in adult female squirrel monkeys.

Laboratory-born, group-housed, ovariectomized adult female squirrel monkeys (Saimiri sciureus) were exposed to feeding conditions in which the availability and accessibility of food were altered. Both high- and variable-demand feeding conditions were utilized. The variable-demand condition required alternating periods of high effort (120% of normal daily intake presented) and low effort (600% of normal daily intake presented) to obtain food for 10-12 weeks. An additional group was exposed solely to the high-demand condition for 10 weeks. Blood samples were obtained weekly, and behavioral observations were conducted daily. In the variable-demand condition, plasma cortisol was elevated above baseline during the periods of high effort. For the constant high-demand group, cortisol was elevated for the duration of the experimental treatment. Contact with other animals, as well as a species-specific inactive posture, decreased as a result of exposure to high demand. Maintenance of body weight indicated that nutritional deprivation did not occur. The imposition of increased food-seeking efforts provides an ecologically relevant and noninvasive method of producing chronic stress in the squirrel monkey.