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Effects of psychosocial stressors on splenic lymphocyte proliferation and natural killer cell activity in the presence or absence of a mouse mammary tumour

University of British Columbia

Weinberg and Emerman (1989) demonstrated that differential housing conditions alter the growth of the transplantable androgen-responsive Shionogi mouse mammary carcinoma (SC115). In addition it was shown that changes in the immune system are influenced both by housing and the presence or absence of tumour. The objective of this thesis was to determine if the immune system and, more specifically, if natural killer (NK) cells may be involved in mediating the effects of differential housing on SC115 tumour growth. In a preliminary study in our laboratory, T lymphocyte proliferation in the spleens of mice in different housing conditions was measured. The initial study of this thesis was designed to replicate these experiments in order to obtain sufficient data for statistical analysis. At the time of tumour-cell injection, mice raised individually from the time of weaning either remained individually housed (II) or were placed in groups of 5 (IG); mice raised in sibling groups of 3 from the time of weaning either remained in their rearing groups (GG) or were separated and housed individually (GI). Three wk after tumour-cell injection, spleens were removed and cells were cultured with or without the mitogen Concanavalin A (Con A) to stimulate proliferation of T lymphocytes. This proliferation was measured by [³H] - thymidine incorporation. In the absence of Con A, there were no differences in spleen cell growth among animals from the 4 housing groups, whether or not they were injected with tumour cells. With Con A stimulation, lymphocyte proliferation was decreased in IG mice. However, changes in response were eliminated in animals injected with tumour cells. The major studies of this thesis focused on the investigation of the role of NK cell activity in modulating tumour growth rate in our model. NK cell lytic activity is modulated by both the presence of a tumour and psychosocial stressors. Further, it has been shown that the immune system responds within days to stressors. In this thesis, NK cell activity at early time points following formation of experimental groups and tumourcell or vehicle injection was examined. First, a protocol to measure splenic NK cell cytolytic activity in our mice was established. Using this protocol, NK cell activity was examined 3 d and 1 wk following tumour-cell or vehicle injection and rehousing. Following vehicle injection, groups did not differ significantly in NK cell activity. All vehicle injected groups were significantly lower in NK cell activity than tumour-cell injected groups and there was no significant change in NK cell activity from 3 d to 1 wk. Significant stimulation of splenic NK cell activity occurred 3 d post-injection of SC115 cells. However, no correlation was observed between the level of splenic NK cell activity and tumour growth rate induced by the housing condition. It was concluded that either splenic NK cell activity does not accurately reflect NK cell activity at the tumour site or that NK cells are not a significant regulator of the differential tumour growth rates seen in this model.

Thesis/Dissertation

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2008-12-18

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http://hdl.handle.net/2429/3168

Physiology

University of British Columbia

UBCV

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