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Infection and Immunity, February 2002, p. 434-443, Vol. 70, No. 2
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.2.434-443.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

CD8+-T-Cell Immunity against Toxoplasma gondii Can Be Induced but Not Maintained in Mice Lacking Conventional CD4+ T Cells

Lori Casciotti,1 Kenneth H. Ely,2 Martha E. Williams,3,4 and Imtiaz A. Khan1,3,4*

Departments of Medicine,1 Physiology,2 Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756,3 Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 701124

Received 12 April 2001/ Returned for modification 11 June 2001/ Accepted 12 October 2001

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-{gamma}) 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-{gamma} 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-{gamma} 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.

* Corresponding author. Mailing address: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112. Phone: (504) 568-7776. Fax: (504) 568-2918. E-mail: ikhan{at}lsuhsc.edu.

Editor: S. H. E. Kaufmann

Infection and Immunity, February 2002, p. 434-443, Vol. 70, No. 2
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.2.434-443.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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