Inhibition of nitric oxide interrupts the accumulation of CD8+ T cells surrounding Plasmodium berghei-infected hepatocytes
| Autor: | Shawn J. Green, Libia F. Scheller, Abdu F. Azad |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Cellular immunity
Plasmodium berghei Immunology In situ hybridization CD8-Positive T-Lymphocytes Biology Nitric Oxide Guanidines Microbiology Nitric oxide chemistry.chemical_compound Rats Inbred BN medicine Animals Cytotoxic T cell Immunity Cellular T lymphocyte biology.organism_classification Virology Molecular biology Malaria Rats Infectious Diseases medicine.anatomical_structure Liver chemistry Hepatocyte Parasitology Nitric Oxide Synthase CD8 Research Article |
| Zdroj: | Infection and Immunity. 65:3882-3888 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.65.9.3882-3888.1997 |
| Popis: | The elimination of liver-stage malaria parasites by nitric oxide (NO)-producing hepatocytes is regulated by T cells. Both CD8+ and CD4+ T cells, which surround infected hepatocytes, are evident by 24 h after sporozoite challenge in Brown Norway rats previously immunized with irradiated Plasmodium berghei sporozoites. While the number of CD4+ T cells remained the same beyond 24 h postchallenge, the number of CD8+ T cells increased three- and sixfold by 31 and 44 h, respectively. This increase in the number of CD8+ T cells correlated with a decrease in the number of intrahepatic parasites. In immunized rats, intrahepatic parasites were reduced in number by 31 h after sporozoite challenge and cleared from the liver by 44 h, as visualized by P. berghei-specific DNA in situ hybridization. If immunized rats were treated with aminoguanidine, a substrate inhibitor of NO synthase, at the time of challenge, liver-stage protection was blocked, as shown by the increase in parasite liver burden. Further histological examination of infected livers from immunized animals treated with aminoguanidine revealed fewer and smaller cellular infiltrates surrounding the infected hepatocytes, and the number of CD8+ T cells that normally accumulate within the infiltrates was drastically reduced. Consequently, the infected hepatocytes were not cleared from the liver. We hypothesize that the early production of NO may promote the influx and/or enhance local proliferation of malaria parasite-specific CD8+ T cells or a CD8+ T-cell subset which is required for parasite clearance. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|