Complete protection against Plasmodium yoelii by adoptive transfer of a CD8+ cytotoxic T-cell clone recognizing sporozoite surface protein 2
S Khusmith, M Sedegah, S L Hoffman, S Khusmith, M Sedegah, S L Hoffman
Abstract
BALB/c mice immunized with irradiated Plasmodium yoelii sporozoites produce antibodies and cytotoxic T lymphocytes against the circumsporozoite protein and against a 140-kDa protein, sporozoite surface protein 2 (PySSP2). Approximately 50% of mice immunized with P815 cells transfected with the gene encoding PySSP2 are protected against malaria, and this protection is reversed by in vivo depletion of CD8+ T cells. To determine if CD8+ T cells against PySSP2 are adequate to protect against malaria in the absence of other malaria-specific immune responses, we produced three CD8+ T-cell clones by stimulating spleen cells from mice immunized with irradiated P. yoelii sporozoites with a mitomycin-treated P815 cell clone transfected with the PySSP2 gene. Adoptive transfer of clone TSLB7 protected 100% of mice against P. yoelii. The second clone protected 58% of mice, and the third clone provided no protection. Clone TSLB7 protected even when administered 3 h after sporozoite inoculation at a time when sporozoites had entered hepatocytes, suggesting that it is recognizing and eliminating infected hepatocytes. These studies demonstrate that cytotoxic T lymphocytes against PySSP2 can protect against P. yoelii sporozoite challenge in the absence of other parasite-specific immune responses.
References
- J Parasitol. 1979 Jun;65(3):414-7
- J Immunol. 1993 Feb 15;150(4):1471-8
- Science. 1986 May 16;232(4752):881-4
- Infect Immun. 1986 Sep;53(3):628-30
- Infect Immun. 1987 Mar;55(3):604-8
- J Immunol Methods. 1987 Nov 23;104(1-2):137-42
- Nature. 1987 Dec 17-23;330(6149):664-6
- J Immunol. 1987 Dec 15;139(12):4192-5
- Proc Natl Acad Sci U S A. 1988 Jan;85(2):573-6
- Proc Natl Acad Sci U S A. 1988 May;85(9):3105-9
- Nature. 1988 Jul 21;334(6179):258-60
- J Immunol. 1988 Sep 1;141(5):1576-81
- J Immunol Methods. 1989 Jan 17;116(2):151-8
- Science. 1989 Jun 2;244(4908):1078-81
- Nature. 1989 Sep 28;341(6240):323-6
- J Exp Med. 1990 Mar 1;171(3):763-73
- J Immunol. 1991 Feb 1;146(3):1020-5
- Science. 1991 Feb 8;251(4994):668-71
- Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3300-4
- Science. 1991 May 3;252(5006):715-8
- J Immunol. 1991 Jun 1;146(11):3971-6
- Bull World Health Organ. 1990;68 Suppl:152-7
- Int Immunol. 1991 Jun;3(6):579-85
- J Exp Med. 1992 Apr 1;175(4):895-905
- Mol Biochem Parasitol. 1992 Jul;53(1-2):45-51
- J Immunol. 1992 Sep 15;149(6):2103-9
- Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9176-80
- J Exp Med. 1980 Jun 1;151(6):1504-13
Source: PubMed