Malaria parasite-specific Th1-like T cells simultaneously reduce parasitemia and promote disease.
CD4+ T cells have been implicated in immunity to the blood stages of malaria and cytokines associated with both monocyte and T cell activation have been implicated in disease. To determine whether specific T cells capable of inhibiting parasite growth can also mediate pathology we have transfused populations of Plasmodium berghei-specific T cells into normal and immunodeficient naive mice. We observed that they could inhibit parasite growth but were unable to save the animals which exhibited significantly greater anaemia and weight loss than control infected animals receiving either no T cells or T cells specific for ovalbumin. T cell-dependent tomour necrosis factor (TNF)alpha was a critical component in both parasite killing and disease promotion. Experiments with blocking antibodies demonstrated that all T-cell mediated antiparasitic immunity and all T-cell mediated weight loss was TNF-dependent. Blocking TNF-alpha in mice that received parasite-specific T cells prolonged the survival of the mice. Nitric oxide demonstrated no antiparasite effect, but was involved in the regulation of T-cell mediated weight loss. The data thus show that while parasite-specific CD4+ T cells can significantly limit parasite growth, such an effect need not be beneficial to the host, and that TNF-alpha and nitric oxide are critical effector molecules operating downstream of parasite-specific T cells in both immunity and disease.
Hirunpetcharat
C
C
The Queensland Institute of Medical Research, Royal Brisbane Hospital, Brisbane 4029, Australia.
Finkelman
F
F
Clark
I A
IA
Good
M F
MF
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D009569:Nitric Oxide / Q000378:metabolism; D018512:Parasitemia / Q000276:immunology* / Q000469:parasitology; D010962:Plasmodium berghei / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide