Splenic gammadelta T cells regulated by CD4+ T cells are required to control chronic Plasmodium chabaudi malaria in the B-cell-deficient mouse.
Little is known about the function and regulation of splenic gammadelta T cells during chronic Plasmodium chabaudi malaria. The splenic gammadelta T-cell population continues to expand, reaching levels equal to 4 times the number of splenocytes in an uninfected mouse. Splenic gammadelta T cells from J(H)-/- mice with chronic malaria expressed Vgamma1+ or Vdelta4+ in the same ratio as uninfected controls with Vgamma1 cells dominating, but the Vgamma2 ratio declined about twofold. Gammadelta 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 gammadelta 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 gammadelta, CD4+, and CD8+ T cells. Following challenge, drug-cured J(H)-/- mice exhibited nearly identical parasitemia time courses as naïve controls. Depletion of either CD4+ T cells or gammadelta T cells from chronically infected J(H)-/- mice by monoclonal antibody treatment resulted in an immediate and significant (P < 0.05) exacerbation of parasitemia coupled with a marked decrease in splenic gammadelta T-cell numbers. The number of CD4+ T cells, in contrast, did not decrease in mice after anti-T-cell receptor gammadelta 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 gammadelta T cells and CD4+ T cells, and (iii) lacks immunological memory.
van der Heyde
Henri C
HC
La Jolla Bioengineering Institute, California 92037, USA.
Batchelder
Joan M
JM
Sandor
Matyas
M
Weidanz
William P
WP
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics; D005260:Female; D008288:Malaria / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016788:Plasmodium chabaudi; D012333:RNA, Messenger / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta