T lymphocytes from mice immunized with irradiated sporozoites eliminate malaria from hepatocytes.
When mice are immunized with radiation-attenuated sporozoites they are solidly protected against sporozoite challenge by an immune response that has been shown to require CD8+ lymphocytes in several strains of mice. The target of this CD8+ T-cell-dependent immunity has not been established. Immune BALB/c mice were shown to develop malaria-specific, CD8+ T-cell-dependent inflammatory infiltrates in their livers after challenge with Plasmodium berghei sporozoites. Spleen cells from immune BALB/c and C57BL/6 mice eliminated hepatocytes infected with the liver stage of P. berghei in vitro. The activity against infected hepatocytes is not inhibited by antibodies to interferon-gamma and is not present in culture supernatants. It is genetically restricted, an indication that malaria antigens on the hepatocyte surface are recognized by immune T-effector cells. Further subunit pre-erythrocytic stage malaria vaccine development will require identification of the antigens recognized by these T cells and a method of immunization that induces such immunity.
Hoffman
S L
SL
Infectious Diseases Department, Naval Medical Research Institute, Bethesda, MD 20889-5055.
Isenbarger
D
D
Long
G W
GW
Sedegah
M
M
Szarfman
A
A
Mellouk
S
S
Ballou
W R
WR
D000818:Animals; D000906:Antibodies; D002478:Cells, Cultured; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000276:immunology* / Q000528:radiation effects; D011994:Recombinant Proteins; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000906:Antibodies; D011994:Recombinant Proteins; D007371:Interferon-gamma