Apoptosis inhibitor expressed by macrophages (AIM) inhibits apoptosis of CD4(+)CD8(+) (CD4/CD8) double-positive thymocytes, and supports the viability of these cells on the thymic selection. However, pleiotropic functions of AIM have been suggested. In this study, heat-killed Corynebacterium parvum (C. parvum) was injected into mice carrying the homozygous mutation (AIM(-/-)) and wild-type (AIM(+/+)) mice, to investigate the role of AIM in the formation of hepatic granulomas. In AIM(-/-) mice, the size and the number of hepatic granulomas were larger, and the resorption of granulomas was more delayed than in AIM(+/+) mice. The production of interleukin-12 was more prominent in AIM(-/-) mice than in AIM(+/+) mice. In the liver of AIM(+/+) mice, expression of AIM messenger ribonucleic acid (mRNA) increased after C. parvum injection. In situ hybridization demonstrated that AIM mRNA was expressed in Kupffer cells and exudate macrophages in the liver, especially in granulomas. Larger numbers of T cells and natural killer T (NKT) cells underwent apoptosis in the granulomas of AIM(-/-) mice, suggesting that AIM prevents apoptosis of NKT cells and T cells in C. parvum-induced inflammation. Recombinant AIM (rAIM) protein significantly inhibited apoptosis of NKT cells and T cells obtained from C. parvum-stimulated livers in vitro. These results indicate that AIM functions to induce resistance to apoptosis within NKT cells and T cells, and supports the host defense in granulomatous inflammation.

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SUMMARYThe age-dependent variation in the proportion and number of lymphocyte subsets was examined at various extrathymic sites, including the liver, small intestine, colon and appendix in mice. In comparison with young mice (4 weeks of age), the number of total lymphocytes yielded by all tested organs was greater in adult (9 weeks) and old (40 weeks) mice. The major lymphocyte subset that expanded with age was interleukin-2 receptor (IL-2R) b + CD3 int cells (50% of them expressed NK1.1) in the liver, whereas it was CD3 + IL-2Rb -NK1.1 -cells at all intraepithelial sites in the intestine. Although NK1.1 + CD3 + cells were present at intraepithelial sites in the intestine, the proportion of this subset was rather low. The ratio of CD4 to CD8 tended to decrease among natural killer T (NKT) cells and T cells at all intraepithelial sites in the intestine with age. A unique population of double-positive CD4 + CD8 + cells in the small intestine increased in old mice. B220 + T cells were found mainly in the appendix and colon, and the proportion of these T cells decreased in old mice. Conventional NKT cells were very few in Ja281 -/--and CD1d -/--mice in the liver, while NKT cells which existed in the appendix remained unchanged even in these mice. This was because unconventional CD8 + NKT cells were present in the intestine. The present results suggest that despite the fact that both the liver and intraepithelial sites in the intestine carry many extrathymic T cells, the distribution of lymphocyte subsets and their age-associated variation are site-specific.