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AIM inhibits apoptosis of T cells and NKT cells in Corynebacterium-induced granuloma formation in mice.

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.

Pubmed ID: 12598318

Authors

  • Kuwata K
  • Watanabe H
  • Jiang SY
  • Yamamoto T
  • Tomiyama-Miyaji C
  • Abo T
  • Miyazaki T
  • Naito M

Journal

The American journal of pathology

Publication Data

March 24, 2003

Associated Grants

None

Mesh Terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Base Sequence
  • DNA Primers
  • Flow Cytometry
  • Gram-Positive Bacterial Infections
  • Granuloma
  • In Situ Hybridization
  • Interleukins
  • Killer Cells, Natural
  • Liver Diseases
  • Mice
  • Mice, Knockout
  • Propionibacterium acnes
  • RNA, Messenger
  • Receptors, Immunologic
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes