Abstract
In mice depleted of B cells from birth by treatment with anti-immunoglobulin M(mu) antibodies, progression from a Th1- to a Th2-regulated immune response during primary infection with Plasmodium chabaudi chabaudi fails to occur. While Th1-type immunity limits parasitemia, in the absence of B cells, chronic low-grade infections persist. Here, we show that reconstituting immune, and to a lesser extent naive, B cells to mice rendered deficient in B-cell function through anti-immunoglobulin M(mu) pretreatment restores the CD4+ T-cell response to the Th2 type later in P. c. chabaudi infection and with it the capacity to eliminate infection. This finding provides clear evidence that B cells are required for switching the balance of immune regulation between CD4+ T cells from Th1 to Th2 during P.c. chabaudi infection and supports the concept that B cells, through antibody production, are needed for effective antimalarial immunity.
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- Abehsira-Amar O., Gibert M., Joliy M., Thèze J., Jankovic D. L. IL-4 plays a dominant role in the differential development of Tho into Th1 and Th2 cells. J Immunol. 1992 Jun 15;148(12):3820–3829. [PubMed] [Google Scholar]
- Gajewski T. F., Pinnas M., Wong T., Fitch F. W. Murine Th1 and Th2 clones proliferate optimally in response to distinct antigen-presenting cell populations. J Immunol. 1991 Mar 15;146(6):1750–1758. [PubMed] [Google Scholar]
- Grun J. L., Weidanz W. P. Immunity to Plasmodium chabaudi adami in the B-cell-deficient mouse. Nature. 1981 Mar 12;290(5802):143–145. doi: 10.1038/290143a0. [DOI] [PubMed] [Google Scholar]
- Hsieh C. S., Macatonia S. E., Tripp C. S., Wolf S. F., O'Garra A., Murphy K. M. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science. 1993 Apr 23;260(5107):547–549. doi: 10.1126/science.8097338. [DOI] [PubMed] [Google Scholar]
- Kopf M., Le Gros G., Bachmann M., Lamers M. C., Bluethmann H., Köhler G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature. 1993 Mar 18;362(6417):245–248. doi: 10.1038/362245a0. [DOI] [PubMed] [Google Scholar]
- Langhorne J., Gillard S., Simon B., Slade S., Eichmann K. Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection. Int Immunol. 1989;1(4):416–424. doi: 10.1093/intimm/1.4.416. [DOI] [PubMed] [Google Scholar]
- Langhorne J. The role of CD4+ T-cells in the immune response to Plasmodium chabaudi. Parasitol Today. 1989 Nov;5(11):362–364. doi: 10.1016/0169-4758(89)90113-0. [DOI] [PubMed] [Google Scholar]
- McLean S. A., Pearson C. D., Phillips R. S. Plasmodium chabaudi: antigenic variation during recrudescent parasitaemias in mice. Exp Parasitol. 1982 Dec;54(3):296–302. doi: 10.1016/0014-4894(82)90038-8. [DOI] [PubMed] [Google Scholar]
- McLean S. A., Pearson C. D., Phillips R. S. Plasmodium chabaudi: relationship between the occurrence of recrudescent parasitaemias in mice and the effective levels of acquired immunity. Exp Parasitol. 1982 Oct;54(2):213–221. doi: 10.1016/0014-4894(82)90129-1. [DOI] [PubMed] [Google Scholar]
- Meding S. J., Langhorne J. CD4+ T cells and B cells are necessary for the transfer of protective immunity to Plasmodium chabaudi chabaudi. Eur J Immunol. 1991 Jun;21(6):1433–1438. doi: 10.1002/eji.1830210616. [DOI] [PubMed] [Google Scholar]
- Moore K. W., O'Garra A., de Waal Malefyt R., Vieira P., Mosmann T. R. Interleukin-10. Annu Rev Immunol. 1993;11:165–190. doi: 10.1146/annurev.iy.11.040193.001121. [DOI] [PubMed] [Google Scholar]
- Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
- Mosmann T. R., Moore K. W. The role of IL-10 in crossregulation of TH1 and TH2 responses. Immunol Today. 1991 Mar;12(3):A49–A53. doi: 10.1016/S0167-5699(05)80015-5. [DOI] [PubMed] [Google Scholar]
- Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
- Parker D. C. T cell-dependent B cell activation. Annu Rev Immunol. 1993;11:331–360. doi: 10.1146/annurev.iy.11.040193.001555. [DOI] [PubMed] [Google Scholar]
- Podoba J. E., Stevenson M. M. CD4+ and CD8+ T lymphocytes both contribute to acquired immunity to blood-stage Plasmodium chabaudi AS. Infect Immun. 1991 Jan;59(1):51–58. doi: 10.1128/iai.59.1.51-58.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scott P. IL-12: initiation cytokine for cell-mediated immunity. Science. 1993 Apr 23;260(5107):496–497. doi: 10.1126/science.8097337. [DOI] [PubMed] [Google Scholar]
- Scott P. Selective differentiation of CD4+ T helper cell subsets. Curr Opin Immunol. 1993 Jun;5(3):391–397. doi: 10.1016/0952-7915(93)90058-z. [DOI] [PubMed] [Google Scholar]
- Stevenson M. M., Tam M. F. Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice. Clin Exp Immunol. 1993 Apr;92(1):77–83. doi: 10.1111/j.1365-2249.1993.tb05951.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Süss G., Eichmann K., Kury E., Linke A., Langhorne J. Roles of CD4- and CD8-bearing T lymphocytes in the immune response to the erythrocytic stages of Plasmodium chabaudi. Infect Immun. 1988 Dec;56(12):3081–3088. doi: 10.1128/iai.56.12.3081-3088.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor-Robinson A. W., Phillips R. S. B cells are required for the switch from Th1- to Th2-regulated immune responses to Plasmodium chabaudi chabaudi infection. Infect Immun. 1994 Jun;62(6):2490–2498. doi: 10.1128/iai.62.6.2490-2498.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor-Robinson A. W., Phillips R. S. Functional characterization of protective CD4+ T-cell clones reactive to the murine malaria parasite Plasmodium chabaudi. Immunology. 1992 Sep;77(1):99–105. [PMC free article] [PubMed] [Google Scholar]
- Taylor-Robinson A. W., Phillips R. S. Protective CD4+ T-cell lines raised against Plasmodium chabaudi show characteristics of either Th1 or Th2 cells. Parasite Immunol. 1993 Jun;15(6):301–310. doi: 10.1111/j.1365-3024.1993.tb00614.x. [DOI] [PubMed] [Google Scholar]
- Taylor-Robinson A. W., Phillips R. S., Severn A., Moncada S., Liew F. Y. The role of TH1 and TH2 cells in a rodent malaria infection. Science. 1993 Jun 25;260(5116):1931–1934. doi: 10.1126/science.8100366. [DOI] [PubMed] [Google Scholar]
- Taylor-Robinson A. W., Phillips R. S. Th1 and Th2 CD4+ T cell clones specific for Plasmodium chabaudi but not for an unrelated antigen protect against blood stage P. chabaudi infection. Eur J Immunol. 1994 Jan;24(1):158–164. doi: 10.1002/eji.1830240124. [DOI] [PubMed] [Google Scholar]
- Taylor-Robinson A. W. Regulation of immunity to malaria: valuable lessons learned from murine models. Parasitol Today. 1995 Sep;11(9):334–342. doi: 10.1016/0169-4758(95)80186-3. [DOI] [PubMed] [Google Scholar]
- Trinchieri G. Interleukin-12: a cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes. Blood. 1994 Dec 15;84(12):4008–4027. [PubMed] [Google Scholar]
- von der Weid T., Kopf M., Köhler G., Langhorne J. The immune response to Plasmodium chabaudi malaria in interleukin-4-deficient mice. Eur J Immunol. 1994 Oct;24(10):2285–2293. doi: 10.1002/eji.1830241004. [DOI] [PubMed] [Google Scholar]
- von der Weid T., Langhorne J. Altered response of CD4+ T cell subsets to Plasmodium chabaudi chabaudi in B cell-deficient mice. Int Immunol. 1993 Oct;5(10):1343–1348. doi: 10.1093/intimm/5.10.1343. [DOI] [PubMed] [Google Scholar]