Involvement of CD8+ T cells in protective immunity against murine blood-stage infection with Plasmodium yoelii 17XL strain.
When developing malaria vaccines, the most crucial step is to elucidate the mechanisms involved in protective immunity against the parasites. We found that CD8(+) T cells contribute to protective immunity against infection with blood-stage parasites of Plasmodium yoelii. Infection of C57BL/6 mice with P. yoelii 17XL was lethal, while all mice infected with a low-virulence strain of the parasite 17XNL acquired complete resistance against re-infection with P. yoelii 17XL. However, the host mice transferred with CD8(+) T cells from mice primed only with P. yoelii 17XNL failed to acquire protective immunity. On the other hand, the irradiated host mice were completely resistant to P. yoelii 17XL infection, showing no grade of parasitemia when adoptively transferred with CD8(+) T cells from immune mice that survived infection with both P. yoelii XNL and, subsequently, P. yoelii 17XL. These protective CD8(+) T cells from immune WT mice had the potential to generate IFN-gamma, perforin (PFN) and granzyme B. When mice deficient in IFN-gamma were used as donor mice for CD8(+) T cells, protective immunity in the host mice was fully abrogated, and the immunity was profoundly attenuated in PFN-deficient mice. Thus, CD8(+) T cells producing IFN-gamma and PFN appear to be involved in protective immunity against infection with blood-stage malaria.
Imai
Takashi
T
Department of Microbiology and Immunology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. t-imai@rcai.riken.jp
Shen
Jianying
J
Chou
Bin
B
Duan
Xuefeng
X
Tu
Liping
L
Tetsutani
Kohhei
K
Moriya
Chikako
C
Ishida
Hidekazu
H
Hamano
Shinjiro
S
Shimokawa
Chikako
C
Hisaeda
Hajime
H
Himeno
Kunisuke
K
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D003289:Convalescence; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D005260:Female; D053804:Granzymes / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D008264:Macrophages / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control; D017780:Malaria Vaccines / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia / Q000276:immunology* / Q000517:prevention & control; D010967:Plasmodium yoelii / Q000276:immunology* / Q000472:pathogenicity; D052899:Pore Forming Cytotoxic Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D011828:Radiation Chimera; D014774:Virulence
D004268:DNA-Binding Proteins; D017780:Malaria Vaccines; D052899:Pore Forming Cytotoxic Proteins; C499308:Rag2 protein, mouse; C483886:perforin, mouse; D007371:Interferon-gamma; D053804:Granzymes; C509214:Gzmb protein, mouse