CD8+-T-Cell Immunity againstToxoplasma gondiiCan Be Induced but Not Maintained in Mice Lacking Conventional CD4+T Cells

Abstract

T-cell immunity is critical for survival of hosts infected with Toxoplasma gondii. Among the cells in the T-cell population, CD8⁺ T cells are considered the major effector cells against this parasite. It is believed that CD4⁺ T cells may be crucial for induction of the CD8⁺-T-cell response against T. gondii. In the present study, CD4^−/− mice were used to evaluate the role of conventional CD4⁺ T cells in the immune response against T. gondii infection. CD4^−/− mice infected with T. gondii exhibited lower gamma interferon (IFN-γ) messages in the majority of their tissues. As a result, mortality due to a hyperinflammatory response was prevented in these animals. Interestingly, T. gondii infection induced a normal antigen-specific CD8⁺-T-cell immune response in CD4^−/− mice. No difference in generation of precursor cytotoxic T lymphocytes (pCTL) or in IFN-γ production by the CD8⁺-T-cell populations from the knockout and wild-type animals was observed. However, the mutant mice were not able to sustain CD8⁺-T-cell immunity. At 180 days after infection, the CD8⁺-T-cell response in the knockout mice was depressed, as determined by pCTL and IFN-γ assays. Loss of CD8⁺-T-cell immunity at this time was confirmed by adoptive transfer experiments. Purified CD8⁺ T cells from CD4^−/− donors that had been immunized 180 days earlier failed to protect the recipient mice against a lethal infection. Our study demonstrated that although CD8⁺-T-cell immunity can be induced in the absence of conventional CD4⁺ T cells, it cannot be maintained without such cells.