Infection and Immunity
Geisel School of Medicine
Toxoplasma gondii remains a serious cause of morbidity and mortality in individuals that are immunosuppressed, patients with AIDS in particular. The cellular immune response, especially by gamma interferon (IFN-γ)-producing CD8+ T cells, is an essential component of protective immunity against the parasite. In the present study the role of CD8+ T cells during the reactivation of Toxoplasma infection in an immunocompromised murine model was evaluated. Chronically infected mice were challenged with LP-BM5 virus, and the kinetics of CD8+ T-cell function was studied. At 10 weeks after viral infection, mice showed obvious signs of systemic illness and began to die. At this stage, CD8+ T cells were unresponsive to antigenic stimulation and unable to kill Toxoplasma-infected targets. IFN-γ production by the CD8+ T cells from dual-infected animals reached background levels, and a dramatic fall in the frequency of precursor cytotoxic T lymphocytes was observed. Histopathological analysis of the tissues demonstrated signs of disseminated toxoplasmosis as a result of reactivation of infection. However, treatment of the dual-infected animals with immune CD8+ T cells at 5 weeks post-LP-BM5 challenge prevented the reactivation of toxoplasmosis, and mice continued to live. Our study for the first time demonstrates a therapeutic role for CD8+ T cells against an opportunistic infection in an immunocompromised state.
Khan IA, Green WR, Kasper LH, Green KA, Schwartzman JD. Immune CD8(+) T cells prevent reactivation of Toxoplasma gondii infection in the immunocompromised host. Infect Immun. 1999;67(11):5869-5876. doi:10.1128/IAI.67.11.5869-5876.1999
Dartmouth Digital Commons Citation
Khan, Imtiaz A.; Green, William R.; Kasper, Lloyd H.; Green, Kathy A.; and Schwartzman, Joseph D., "Immune CD8+ T Cells Prevent Reactivation of Toxoplasma gondii Infection in the Immunocompromised Host" (1999). Dartmouth Scholarship. 985.