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CD4⁺ T Cells in the Pathogenesis of Murine Ocular Toxoplasmosis

Fangli Lu, Shiguang Huang,^, and Lloyd H. Kasper^*

Department of Medicine and Microbiology, Dartmouth Medical School, Lebanon, New Hampshire

Received 10 March 2004/ Returned for modification 22 April 2004/ Accepted 15 June 2004

The role of CD4⁺ T cells in the pathogenesis of ocular toxoplasmosis was investigated in murine models utilizing inbred C57BL/6 mice deficient either in CD4⁺, CD8⁺, or B cells (µMT). Severe necrosis and inflammation with replicating parasites were observed in the eyes of control mice after primary ocular infection, and near-normal histology with few tachyzoites was observed in the eyes of mice immunized intraperitoneally with the avirulent ts-4 strain followed by intraocular challenge with the RH strain of Toxoplasma gondii. In contrast, mild inflammation without evidence of necrosis associated with increased parasite burdens were observed in the eyes of CD4 knockout (KO) mice after both primary ocular infection and challenge with RH tachyzoites. CD8 KO mice, as well as µMT mice, demonstrated increased ocular necrosis in response to either primary ocular infection or challenge. The parasite burden was increased in the eyes of both CD8 KO and µMT mice in which the parasite load was even higher. As expected, there were no increases in the levels of immunoglobulin G in serum or aqueous humor in µMT mice, and there was no increase in the levels of gamma interferon and tumor necrosis factor alpha in the sera of CD4 KO mice after both infection and challenge. These results suggest that the ocular inflammatory response to the parasite is mediated primarily by the CD4⁺-T-cell response. CD8⁺ T cells and B cells may play an important role in limiting tachyzoite proliferation in the eyes. Mice deficient in CD8⁺ CD4⁺ T cells or B cells exhibit diminished vaccine-induced resistance and increased ocular parasite burden after challenge.

Editor: W. A. Petri, Jr.

Present address: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20850.

Present address: Jinan University School of Medicine, Guangzhou 510632, China.

This article has been cited by other articles:

• Lu, F., Huang, S., Hu, M. S., Kasper, L. H. (2005). Experimental Ocular Toxoplasmosis in Genetically Susceptible and Resistant Mice. Infect. Immun. 73: 5160-5165 [Abstract] [Full Text]