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.
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.
Ciavarra
R P
RP
Department of Microbiology and Immunology, Eastern Virginia Medical School, Norfolk 23501, USA.
Buhrer
K
K
Van Rooijen
N
N
Tedeschi
B
B
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D004002:Clodronic Acid / Q000008:administration & dosage; D007114:Immunization; D007274:Injections, Intraperitoneal; D008081:Liposomes; D008213:Lymphocyte Activation; D008264:Macrophages / Q000145:classification / Q000276:immunology* / Q000821:virology*; D008670:Metals / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
D008081:Liposomes; D008670:Metals; D004002:Clodronic Acid