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Infection and Immunity, May 2006, p. 2717-2725, Vol. 74, No. 5
0019-9567/06/$08.00+0 doi:10.1128/IAI.74.5.2717-2725.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

T Cells Regulated by CD4+ T Cells Are Required To Control Chronic Plasmodium chabaudi Malaria in the B-Cell-Deficient Mouse
La Jolla Bioengineering Institute, La Jolla, California 92037,1 Departments of Medical Microbiology and Immunology,2 Pathology, University of Wisconsin Medical School, Madison, Wisconsin 537063
Received 21 December 2005/ Returned for modification 25 January 2006/ Accepted 11 February 2006
Little is known about the function and regulation of splenic 
T cells during chronic Plasmodium chabaudi malaria. The splenic 
T-cell population continues to expand, reaching levels equal to 4 times the number of splenocytes in an uninfected mouse. Splenic 
T cells from JH/ mice with chronic malaria expressed V
1+ or V
4+ in the same ratio as uninfected controls with V
1 cells dominating, but the V
2 ratio declined about twofold. 
T cells from G8 mice specific for the TL antigen increased only 2-fold in number, compared with 10-fold in BALB/c controls, but G8 
T cells failed to express the B220 activation marker. Elimination of the parasite by drug treatment caused a slow depletion in the number of splenic 
, CD4+, and CD8+ T cells. Following challenge, drug-cured JH/ mice exhibited nearly identical parasitemia time courses as naïve controls. Depletion of either CD4+ T cells or 
T cells from chronically infected JH/ mice by monoclonal antibody treatment resulted in an immediate and significant (P < 0.05) exacerbation of parasitemia coupled with a marked decrease in splenic 
T-cell numbers. The number of CD4+ T cells, in contrast, did not decrease in mice after anti-T-cell receptor 
treatment. The results indicate that cell-mediated immunity against blood-stage malarial parasites during chronic malaria (i) requires the continued presence of blood-stage parasites to remain functional, (ii) is dependent upon both 
T cells and CD4+ T cells, and (iii) lacks immunological memory.
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