Splenic [gamma][delta] T Cells Regulated by CD4⁺ T Cells Are Required To Control Chronic Plasmodium chabaudi Malaria in the B-Cell-Deficient Mouse
2006
Heyde, Henri C van der | Batchelder, Joan M. | Sandor, Matyas | Weidanz, William P.
Little is known about the function and regulation of splenic [gamma][delta] T cells during chronic Plasmodium chabaudi malaria. The splenic [gamma][delta] T-cell population continues to expand, reaching levels equal to 4 times the number of splenocytes in an uninfected mouse. Splenic [gamma][delta] T cells from J[subscript H][superscript -/-] mice with chronic malaria expressed V[gamma]1⁺ or V[delta]4⁺ in the same ratio as uninfected controls with V[gamma]1 cells dominating, but the V[gamma]2 ratio declined about twofold. [gamma][delta] 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 [gamma][delta] 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 [gamma][delta], CD4⁺, and CD8⁺ T cells. Following challenge, drug-cured J[subscript H][superscript -/-] mice exhibited nearly identical parasitemia time courses as naïve controls. Depletion of either CD4⁺ T cells or [gamma][delta] T cells from chronically infected J[subscript H][superscript -/-] mice by monoclonal antibody treatment resulted in an immediate and significant (P < 0.05) exacerbation of parasitemia coupled with a marked decrease in splenic [gamma][delta] T-cell numbers. The number of CD4⁺ T cells, in contrast, did not decrease in mice after anti-T-cell receptor [gamma][delta] 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 [gamma][delta] T cells and CD4⁺ T cells, and (iii) lacks immunological memory.
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