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.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Charoenvit Y., Collins W. E., Jones T. R., Millet P., Yuan L., Campbell G. H., Beaudoin R. L., Broderson J. R., Hoffman S. L. Inability of malaria vaccine to induce antibodies to a protective epitope within its sequence. Science. 1991 Feb 8;251(4994):668–671. doi: 10.1126/science.1704150. [DOI] [PubMed] [Google Scholar]
- Charoenvit Y., Leef M. F., Yuan L. F., Sedegah M., Beaudoin R. L. Characterization of Plasmodium yoelii monoclonal antibodies directed against stage-specific sporozoite antigens. Infect Immun. 1987 Mar;55(3):604–608. doi: 10.1128/iai.55.3.604-608.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Charoenvit Y., Mellouk S., Cole C., Bechara R., Leef M. F., Sedegah M., Yuan L. F., Robey F. A., Beaudoin R. L., Hoffman S. L. Monoclonal, but not polyclonal, antibodies protect against Plasmodium yoelii sporozoites. J Immunol. 1991 Feb 1;146(3):1020–1025. [PubMed] [Google Scholar]
- Curry R. C., Kiener P. A., Spitalny G. L. A sensitive immunochemical assay for biologically active MuIFN-gamma. J Immunol Methods. 1987 Nov 23;104(1-2):137–142. doi: 10.1016/0022-1759(87)90497-2. [DOI] [PubMed] [Google Scholar]
- Ferreira A., Schofield L., Enea V., Schellekens H., van der Meide P., Collins W. E., Nussenzweig R. S., Nussenzweig V. Inhibition of development of exoerythrocytic forms of malaria parasites by gamma-interferon. Science. 1986 May 16;232(4752):881–884. doi: 10.1126/science.3085218. [DOI] [PubMed] [Google Scholar]
- Hedstrom R. C., Campbell J. R., Leef M. L., Charoenvit Y., Carter M., Sedegah M., Beaudoin R. L., Hoffman S. L. A malaria sporozoite surface antigen distinct from the circumsporozoite protein. Bull World Health Organ. 1990;68 (Suppl):152–157. [PMC free article] [PubMed] [Google Scholar]
- Hoffman S. L., Isenbarger D., Long G. W., Sedegah M., Szarfman A., Waters L., Hollingdale M. R., van der Meide P. H., Finbloom D. S., Ballou W. R. Sporozoite vaccine induces genetically restricted T cell elimination of malaria from hepatocytes. Science. 1989 Jun 2;244(4908):1078–1081. doi: 10.1126/science.2524877. [DOI] [PubMed] [Google Scholar]
- Khusmith S., Charoenvit Y., Kumar S., Sedegah M., Beaudoin R. L., Hoffman S. L. Protection against malaria by vaccination with sporozoite surface protein 2 plus CS protein. Science. 1991 May 3;252(5006):715–718. doi: 10.1126/science.1827210. [DOI] [PubMed] [Google Scholar]
- Kumar S., Miller L. H., Quakyi I. A., Keister D. B., Houghten R. A., Maloy W. L., Moss B., Berzofsky J. A., Good M. F. Cytotoxic T cells specific for the circumsporozoite protein of Plasmodium falciparum. Nature. 1988 Jul 21;334(6179):258–260. doi: 10.1038/334258a0. [DOI] [PubMed] [Google Scholar]
- Maheshwari R. K., Czarniecki C. W., Dutta G. P., Puri S. K., Dhawan B. N., Friedman R. M. Recombinant human gamma interferon inhibits simian malaria. Infect Immun. 1986 Sep;53(3):628–630. doi: 10.1128/iai.53.3.628-630.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malik A., Egan J. E., Houghten R. A., Sadoff J. C., Hoffman S. L. Human cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3300–3304. doi: 10.1073/pnas.88.8.3300. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mellouk S., Green S. J., Nacy C. A., Hoffman S. L. IFN-gamma inhibits development of Plasmodium berghei exoerythrocytic stages in hepatocytes by an L-arginine-dependent effector mechanism. J Immunol. 1991 Jun 1;146(11):3971–3976. [PubMed] [Google Scholar]
- Mellouk S., Maheshwari R. K., Rhodes-Feuillette A., Beaudoin R. L., Berbiguier N., Matile H., Miltgen F., Landau I., Pied S., Chigot J. P. Inhibitory activity of interferons and interleukin 1 on the development of Plasmodium falciparum in human hepatocyte cultures. J Immunol. 1987 Dec 15;139(12):4192–4195. [PubMed] [Google Scholar]
- Mosmann T. R., Fong T. A. Specific assays for cytokine production by T cells. J Immunol Methods. 1989 Jan 17;116(2):151–158. doi: 10.1016/0022-1759(89)90198-1. [DOI] [PubMed] [Google Scholar]
- Pacheco N. D., Strome C. P., Mitchell F., Bawden M. P., Beaudoin R. L. Rapid, large-scale isolation of Plasmodium berghei sporozoites from infected mosquitoes. J Parasitol. 1979 Jun;65(3):414–417. [PubMed] [Google Scholar]
- Potocnjak P., Yoshida N., Nussenzweig R. S., Nussenzweig V. Monovalent fragments (Fab) of monoclonal antibodies to a sporozoite surface antigen (Pb44) protect mice against malarial infection. J Exp Med. 1980 Jun 1;151(6):1504–1513. doi: 10.1084/jem.151.6.1504. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rodrigues M. M., Cordey A. S., Arreaza G., Corradin G., Romero P., Maryanski J. L., Nussenzweig R. S., Zavala F. CD8+ cytolytic T cell clones derived against the Plasmodium yoelii circumsporozoite protein protect against malaria. Int Immunol. 1991 Jun;3(6):579–585. doi: 10.1093/intimm/3.6.579. [DOI] [PubMed] [Google Scholar]
- Rodrigues M., Nussenzweig R. S., Romero P., Zavala F. The in vivo cytotoxic activity of CD8+ T cell clones correlates with their levels of expression of adhesion molecules. J Exp Med. 1992 Apr 1;175(4):895–905. doi: 10.1084/jem.175.4.895. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rogers W. O., Malik A., Mellouk S., Nakamura K., Rogers M. D., Szarfman A., Gordon D. M., Nussler A. K., Aikawa M., Hoffman S. L. Characterization of Plasmodium falciparum sporozoite surface protein 2. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9176–9180. doi: 10.1073/pnas.89.19.9176. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rogers W. O., Rogers M. D., Hedstrom R. C., Hoffman S. L. Characterization of the gene encoding sporozoite surface protein 2, a protective Plasmodium yoelii sporozoite antigen. Mol Biochem Parasitol. 1992 Jul;53(1-2):45–51. doi: 10.1016/0166-6851(92)90005-5. [DOI] [PubMed] [Google Scholar]
- Romero P., Maryanski J. L., Corradin G., Nussenzweig R. S., Nussenzweig V., Zavala F. Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature. 1989 Sep 28;341(6240):323–326. doi: 10.1038/341323a0. [DOI] [PubMed] [Google Scholar]
- Rénia L., Grillot D., Marussig M., Corradin G., Miltgen F., Lambert P. H., Mazier D., Del Giudice G. Effector functions of circumsporozoite peptide-primed CD4+ T cell clones against Plasmodium yoelii liver stages. J Immunol. 1993 Feb 15;150(4):1471–1478. [PubMed] [Google Scholar]
- Schofield L., Villaquiran J., Ferreira A., Schellekens H., Nussenzweig R., Nussenzweig V. Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature. 1987 Dec 17;330(6149):664–666. doi: 10.1038/330664a0. [DOI] [PubMed] [Google Scholar]
- Schumacher J. H., O'Garra A., Shrader B., van Kimmenade A., Bond M. W., Mosmann T. R., Coffman R. L. The characterization of four monoclonal antibodies specific for mouse IL-5 and development of mouse and human IL-5 enzyme-linked immunosorbent. J Immunol. 1988 Sep 1;141(5):1576–1581. [PubMed] [Google Scholar]
- Takahashi H., Cohen J., Hosmalin A., Cease K. B., Houghten R., Cornette J. L., DeLisi C., Moss B., Germain R. N., Berzofsky J. A. An immunodominant epitope of the human immunodeficiency virus envelope glycoprotein gp160 recognized by class I major histocompatibility complex molecule-restricted murine cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1988 May;85(9):3105–3109. doi: 10.1073/pnas.85.9.3105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weiss W. R., Berzofsky J. A., Houghten R. A., Sedegah M., Hollindale M., Hoffman S. L. A T cell clone directed at the circumsporozoite protein which protects mice against both Plasmodium yoelii and Plasmodium berghei. J Immunol. 1992 Sep 15;149(6):2103–2109. [PubMed] [Google Scholar]
- Weiss W. R., Mellouk S., Houghten R. A., Sedegah M., Kumar S., Good M. F., Berzofsky J. A., Miller L. H., Hoffman S. L. Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes. J Exp Med. 1990 Mar 1;171(3):763–773. doi: 10.1084/jem.171.3.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weiss W. R., Sedegah M., Beaudoin R. L., Miller L. H., Good M. F. CD8+ T cells (cytotoxic/suppressors) are required for protection in mice immunized with malaria sporozoites. Proc Natl Acad Sci U S A. 1988 Jan;85(2):573–576. doi: 10.1073/pnas.85.2.573. [DOI] [PMC free article] [PubMed] [Google Scholar]