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Infection and Immunity, November 1999, p. 5869-5876, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Immune CD8+ T Cells Prevent Reactivation of Toxoplasma gondii Infection in the Immunocompromised Host

Imtiaz A. Khan,1,* William R. Green,2 Lloyd H. Kasper,1 Kathy A. Green,1 and Joseph D. Schwartzman3

Departments of Medicine,1 Microbiology,2 and Pathology,3 Dartmouth Medical School, Lebanon, New Hampshire 03756

Received 1 April 1999/Returned for modification 27 May 1999/Accepted 24 August 1999

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-gamma )-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-gamma 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.

* Corresponding author. Mailing address: Department of Medicine, Dartmouth Medical School, HB7506, One Medical Center Dr., Lebanon, NH 03756. Phone: (603) 650-8706. Fax: (603) 650-6841. E-mail: Imtiaz.Khan{at}dartmouth.edu.

Infection and Immunity, November 1999, p. 5869-5876, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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