T cell priming against vesicular stomatitis virus analyzed in situ: red pulp macrophages, but neither marginal metallophilic nor marginal zone macrophages, are required for priming CD4+ and CD8+ T cells.

Abstract

Since extensive degradation may be required to present complex Ags, we addressed whether macrophages (M phi) might function as APC for anti-viral cell-mediated immune responses. To study this question, murine splenic M phi were depleted by i.p. administration of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP-liposomes or clodronate-liposomes) before priming mice with vesicular stomatitis virus (VSV). Cl2MDP-liposome treatment resulted in the rapid (1-day) depletion of splenic M phi that was associated with a suppression of the ability of M phi-deficient mice to generate secondary anti-VSV CTL and Th cell proliferative responses in vitro. Control studies demonstrated that splenic dendritic cells were not adversely affected by treatment with Cl2MDP-liposomes. To assess the contribution of splenic M phi subpopulations to T cell priming against this virus, priming was delayed following treatment with Cl2MDP-liposomes until specific M phi subsets had repopulated the spleen. This analysis revealed that repopulation by red pulp M phi, but not with other splenic M phi subsets, was associated with the ability to mount normal secondary CTL and Th cell responses against VSV. Depletion of splenic, but not resident, peritoneal M phi by i.v. injection of Cl2MDP-liposomes did not rescue T cell priming in VSV-infected mice. Thus, only red pulp M phi, and not other splenic or peritoneal M phi populations, are necessary for T cell priming to VSV, a biochemically complex Ag.

• Authors: R P Ciavarra, K Buhrer, N Van Rooijen, B Tedeschi
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 158 Issue 4 Pg. 1749-55 (Feb 15 1997) ISSN: 0022-1767 [Print] United States
• PMID: 9029112 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Liposomes
• Metals
• Clodronic Acid

Topics

• Animals
• CD4-Positive T-Lymphocytes (immunology, virology)
• CD8-Positive T-Lymphocytes (immunology, virology)
• Clodronic Acid (administration & dosage)
• Immunization
• Injections, Intraperitoneal
• Liposomes
• Lymphocyte Activation
• Macrophages (classification, immunology, virology)
• Metals (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Spleen (cytology, immunology, virology)
• Vesicular stomatitis Indiana virus (immunology)