CD4+ T cells in the pathogenesis of murine ocular toxoplasmosis.
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 (microMT). 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 microMT 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 microMT 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 microMT 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.
Department of Medicine and Microbiology, Dartmouth Medical School, Rubin Bldg. 7, Lebanon, NH 03756, USA.
Fangli
F
Lu
Shiguang
S
Huang
Lloyd H
LH
Kasper
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000235:genetics; D005123:Eye / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014122:Toxoplasma / Q000276:immunology* / Q000472:pathogenicity*; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000503:physiopathology*; D014126:Toxoplasmosis, Ocular / Q000276:immunology / Q000503:physiopathology*
D000913:Antibodies, Protozoan; D015704:CD4 Antigens; D016827:CD8 Antigens