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Infection and Immunity, March 2000, p. 1312-1318, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The CD40/CD40 Ligand Interaction Is Required for Resistance to Toxoplasmic Encephalitis

Gaby Reichmann,1,dagger William Walker,2 Eric N. Villegas,1 Linden Craig,1 Guifang Cai,1 James Alexander,2 and Christopher A. Hunter1,*

Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6050,1 and Department of Immunology, The Strathclyde Institute of Biomedical Sciences, University of Strathclyde, Glasgow, G4 ONR, Scotland2

Received 27 October 1999/Returned for modification 2 December 1999/Accepted 16 December 1999

Since the CD40/CD40 ligand (CD40L) interaction is involved in the regulation of macrophage production of interleukin 12 (IL-12) and T-cell production of gamma interferon (IFN-gamma ), effector cell functions associated with resistance to Toxoplasma gondii, the role of CD40L in immunity to this parasite was assessed. Infection of C57BL/6 mice with T. gondii results in an upregulation of CD40 expression on accessory cell populations at local sites of infection as well as in lymphoid tissues. Splenocytes from C57BL/6 mice infected with T. gondii for 5 days produced high levels of IL-12 and IFN-gamma when stimulated with toxoplasma lysate antigen, and blocking CD40L did not significantly alter the production of IFN-gamma or IL-12 by these cells. Similar results were observed with splenocytes and mononuclear cells isolated from the brains of chronically infected mice. Interestingly, although CD40L-/- mice infected with T. gondii produced less IL-12 than wild-type mice, they produced comparable levels of IFN-gamma but succumbed to toxoplasmic encephalitis 4 to 5 weeks after infection. The inability of CD40L-/- mice to control parasite replication in the brain correlated with the ability of soluble CD40L, in combination with IFN-gamma , to activate macrophages in vitro to control replication of T. gondii. Together, these results identify an important role for the CD40/CD40L interaction in resistance to T. gondii. However, this interaction may be more important in the control of parasite replication in the brain rather than the generation of protective T-cell responses during toxoplasmosis.

* Corresponding author. Mailing address: Department of Pathobiology, University of Pennsylvania, 3800 Spruce St., Philadelphia, PA 19104-6050. Phone: (215) 573-7772. Fax: (215) 573-7023. E-mail: chunter{at}phl.vet.upenn.edu.

dagger Present address: Institute for Medical Microbiology and Virology, Heinrich-Heine-University, 40225 Dusseldorf, Germany.

Infection and Immunity, March 2000, p. 1312-1318, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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