Splenic γδ T Cells Regulated by CD4+T Cells Are Required To Control ChronicPlasmodium chabaudiMalaria in the B-Cell-Deficient Mouse

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Abstract
Little is known about the function and regulation of splenic γδ T cells during chronicPlasmodium chabaudimalaria. The splenic γδ T-cell population continues to expand, reaching levels equal to 4 times the number of splenocytes in an uninfected mouse. Splenic γδ T cells from JH−/−mice with chronic malaria expressed Vγ1+or Vδ4+in the same ratio as uninfected controls with Vγ1 cells dominating, but the Vγ2 ratio declined about twofold. γδ 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 γδ 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 γδ, 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 γδ 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 γδ T-cell numbers. The number of CD4+T cells, in contrast, did not decrease in mice after anti-T-cell receptor γδ 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 γδ T cells and CD4+T cells, and (iii) lacks immunological memory.