Production of interleukin 10 during malaria caused by lethal and nonlethal variants of Plasmodium yoelii yoelii.
We investigated the induction of T-helper cell subsets during the course of lethal or nonlethal bloodstage Plasmodium yoelii 17X infection in C57BL/6 mice, which are relatively susceptible to these intraerythrocytic parasites. C57BL/6 mice infected with the nonlethal variant (PyNL) showed a moderate level of parasitemia and resolution of primary acute infection by week 4. Mice infected with the lethal variant (PyL) developed fulminating parasitemia and ultimately died. T-helper subset function was assessed during infection by determining the kinetics of in vitro production of the Th1-derived cytokine interferon-gamma (IFN-gamma) and the Th2-derived cytokine interleukin 10 (IL-10) by means of bioassay and enzyme-linked immunosorbent assay (ELISA), respectively. Spleen cells obtained from mice infected with PyL within the 1st week of infection produced high levels of IL-10 and IFN-gamma in response to malaria antigen. IL-10 also appeared in sera from PyL-infected mice at the same time at which the in vitro IL-10 response peaked. In contrast, spleen cells from mice infected with PyNL failed to produce IL-10 during the course of infection. CD4+ T-lymphocytes from mice infected with the lethal variant were a major source of IL-10, although non T-cells were also involved in the production of IL-10 during this malaria infection. In addition, the initial burst of IL-10 in response to malaria antigens was seen concomitantly with the production of IFN-gamma within the 1st week of infection. These results indicate that both Th1 and Th2 subsets of T-helper lymphocytes are activated during infection with the lethal variant of P. yoelii and support the contention of other investigators that a strong Th2 response early in infection is associated with the lethal outcome of malaria.
Kobayashi
F
F
Department of Tropical Diseases and Parasitology, Kyorin University School of Medicine, Tokyo, Japan. CXJ17045@niftyserve.or.jp
Morii
T
T
Matsui
T
T
Fujino
T
T
Watanabe
Y
Y
Weidanz
W P
WP
Tsuji
M
M
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D014644:Genetic Variation; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology*; D008212:Lymphocyte Depletion; D008288:Malaria / Q000097:blood / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010967:Plasmodium yoelii / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014774:Virulence
D016753:Interleukin-10; D007371:Interferon-gamma