The influence of a gastrointestinal microflora on natural killer cell activity.

Abstract

These studies demonstrate that the natural cytotoxicity of BALB/c mouse spleen cells for 51Cr-labeled YAC-1 cells can be significantly enhanced by microorganisms in the alimentary tract. Spleen cells from germfree BALB/c mice, euthymic, athymic, or non-nude background (+/+), had natural cell-mediated cytotoxicity for YAC-1 cells. Intestinal colonization with a few (flora-defined) or many (complex flora-conventionalized) microorganisms significantly enhanced natural cell-mediated cytotoxicity of athymic and euthymic mice over their germfree counterparts. Conversely, colonization of the alimentary tract of athymic and euthymic germfree mice with a pure culture of Candida albicans or colonization with Candida and a Bacillus sp. did not enhance natural cell-mediated cytotoxic activity over germfree levels. Spleen cells from germfree athymic mice were significantly more cytotoxic than spleen cells from germfree BALB/c mice that did not carry the nude gene (ie, +/+). In the germfree or gnotobiotic state, no difference in natural killer cell activity was evident between athymic (nu/nu) and heterozygous (+/nu) littermate mice; however, athymic (nu/nu) flora-defined or conventionalized mouse spleen cells were significantly more cytotoxic for YAC-1 cells than splenocytes from flora-defined or conventionalized heterozygous (+/nu) littermates. Spleen cells from BALB/c mice that were athymic (nu/nu) and colonized with a complex microbial flora (ie, conventionalized) had the highest percentage of cytotoxicity, at three different effector to target ratios, for YAC-1 cells. These studies indicate that the intestinal microflora can alter murine natural cell-mediated cytotoxicity.