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Infection and Immunity, October 2004, p. 5768-5774, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.5768-5774.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

CD28 Costimulation Is Required for the Expression of T-Cell-Dependent Cell-Mediated Immunity against Blood-Stage Plasmodium chabaudi Malaria Parasites

Thomas Rummel,1 Joan Batchelder,1 Patrick Flaherty,1 GayeLyn LaFleur,1 Payal Nanavati,2 James M. Burns,2 and William P. Weidanz1*

Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin,1 Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania2

Received 20 May 2004/ Returned for modification 24 June 2004/ Accepted 10 July 2004

Mice suppress the parasitemia of acute blood-stage Plasmodium chabaudi malaria by an antibody- or T-cell-dependent cell-mediated mechanism of immunity (AMI and CMI, respectively) or by both mechanisms. To determine whether CD28 costimulation is required for expression of these polar immune responses, we first compared the time courses of P. chabaudi malaria in CD28-deficient (CD28–/–) and CD28-intact (CD28+/+) mice. Acute infections in both knockout (KO) and control mice followed similar time courses, with the period of descending parasitemia being prolonged ~2 weeks in KO mice followed by intermittent low-grade chronic parasitemia. Infected CD28–/– mice produced primarily the immunoglobulin M antibody, which upon passive transfer provided partial protection against P. chabaudi challenge, suggesting that the elimination of blood-stage parasites by CD28–/– mice was achieved by AMI. To determine whether CD28–/– costimulation is required for the expression of CMI against the parasite, we compared the time courses of parasitemia in B-cell-deficient double-KO (JH–/– x CD28–/–) mice and control (JH–/– x CD28+/+) mice. Whereas control mice suppressed parasitemia to subpatent levels within ~2 weeks postinoculation, double-KO mice developed high levels of parasitemia of long-lasting duration. Although not required for the suppression of acute P. chabaudi parasitemia by AMI, CD28 costimulation is essential for the elimination of blood-stage parasites by CMI.


* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, 1300 University Ave., Madison, WI 53706. Phone: (608) 262-9027. Fax: (608) 262-8418. E-mail: wweidanz{at}wisc.edu.

Editor: W. A. Petri, Jr.


Infection and Immunity, October 2004, p. 5768-5774, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.5768-5774.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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