Immune CD8+ T cells prevent reactivation of Toxoplasma gondii infection inthe immunocompromised host

Toxoplasma gondii remains a serious cause of morbidity and mortality in ind ividuals that are immunosuppressed, patients with AIDS in particular. The c ellular immune response, especially by gamma interferon (IFN-gamma)-produci ng 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 r eactivation of Toxoplasma infection in an immunocompromised murine model wa s evaluated, Chronically infected mice were challenged with LP-BM5 virus, a nd the kinetics of CD8(+) T-cell function was studied. At 10 weeks after vi ral infection, mice showed obvious signs of systemic illness and began to d ie, At this stage, CD8(+) T cells were unresponsive to antigenic stimulatio n and unable to kill Toxoplasma-infected targets. IFN-gamma production by t he 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 d isseminated toxoplasmosis as a result of reactivation of infection. However , treatment of the dual-infected animals with immune CD8(+) T cells at 5 we eks post-LP-BM5 challenge prevented the reactivation of toxoplasmosis, and mice continued to live. Our study for the first time demonstrates a therape utic role for CD8(+) T cells against an opportunistic infection in an immun ocompromised state.