Abstract
We have examined the possibility that hyperthermia, such as that occurring during fever, may benefit the immune response. The effect of temperature on the in vitro immune response of unprimed murine spleen cells against the antigen sheep erythrocytes was tested. Hyperthermia potently augmented the plaque-forming cell response. Temperature- sensitive events occurred early in the culture period. Subsets of lymphocytes were independently assessed for effects of temperature on their activation and function. We showed that the beneficial effect of elevated temperature on the plaque-forming cell response probably occurs during the priming stage of T helper cells, and neither improves the delivery of help or the activation of B cells, nor impairs suppressor T cell generation or function. We propose that this powerful immunopotentiating effect of hyperthermia may account for the selective value of the fever response. This suggests taht the monokine interleukin 1, which is the endogenous mediator of fever, may promote immune responses both through a direct action on lymphocytes, and indirectly by an action on the central nervous system resulting in fever.
Full Text
The Full Text of this article is available as a PDF (740.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ATKINS E. Pathogenesis of fever. Physiol Rev. 1960 Jul;40:580–646. doi: 10.1152/physrev.1960.40.3.580. [DOI] [PubMed] [Google Scholar]
- ATKINS E., WOOD W. B., Jr Studies on the pathogenesis of fever. II. Identification of an endogenous pyrogen in the blood stream following the injection of typhoid vaccine. J Exp Med. 1955 Nov 1;102(5):499–516. doi: 10.1084/jem.102.5.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ashman R. B., Nahmias A. J. Enhancement of human lymphocyte responses to phytomitogens in vitro by incubation at elevated temperatures. Clin Exp Immunol. 1977 Sep;29(3):464–467. [PMC free article] [PubMed] [Google Scholar]
- Atkins E., Feldman J. D., Francis L., Hursh E. Studies on the mechanism of fever accompanying delayed hypersensitivity. The role of the sensitized lymphocyte. J Exp Med. 1972 May 1;135(5):1113–1132. doi: 10.1084/jem.135.5.1113. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bernheim H. A., Block L. H., Atkins E. Fever: pathogenesis, pathophysiology, and purpose. Ann Intern Med. 1979 Aug;91(2):261–270. doi: 10.7326/0003-4819-91-2-261. [DOI] [PubMed] [Google Scholar]
- Bodel P., Miller H. Pyrogen from mouse macrophages causes fever in mice. Proc Soc Exp Biol Med. 1976 Jan;151(1):93–96. doi: 10.3181/00379727-151-39150. [DOI] [PubMed] [Google Scholar]
- Covert J. B., Reynolds W. W. Survival value of fever in fish. Nature. 1977 May 5;267(5606):43–45. doi: 10.1038/267043a0. [DOI] [PubMed] [Google Scholar]
- Cranston W. I., Hellon R. F., Townsend Y. Suppression of fever in rabbits by a protein synthesis inhibitor, anisomycin. J Physiol. 1980 Aug;305:337–344. doi: 10.1113/jphysiol.1980.sp013367. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cunningham A. J., Szenberg A. Further improvements in the plaque technique for detecting single antibody-forming cells. Immunology. 1968 Apr;14(4):599–600. [PMC free article] [PubMed] [Google Scholar]
- Duff G. W., Atkins E. The detection of endotoxin by in vitro production of endogenous pyrogen: comparison with limulus amebocyte lysate gelation. J Immunol Methods. 1982 Aug 13;52(3):323–331. doi: 10.1016/0022-1759(82)90004-7. [DOI] [PubMed] [Google Scholar]
- Dutton R. W. Separate signals for the initiation of proliferation and differentiation in the b cell response to antigen. Transplant Rev. 1975;23:66–77. doi: 10.1111/j.1600-065x.1975.tb00149.x. [DOI] [PubMed] [Google Scholar]
- Eardley D. D., Gershon R. K. Induction of specific suppressor T cells in vitro. J Immunol. 1976 Jul;117(1):313–318. [PubMed] [Google Scholar]
- Gershon R. K., Eardley D. D., Durum S., Green D. R., Shen F. W., Yamauchi K., Cantor H., Murphy D. B. Contrasuppression. A novel immunoregulatory activity. J Exp Med. 1981 Jun 1;153(6):1533–1546. doi: 10.1084/jem.153.6.1533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keller D. M., Swierkosz J. E., Marrack P., Kappler J. W. Two types of functionally distinct, synergizing helper T cells. J Immunol. 1980 Mar;124(3):1350–1359. [PubMed] [Google Scholar]
- Kelley P. M., Schlesinger M. J. The effect of amino acid analogues and heat shock on gene expression in chicken embryo fibroblasts. Cell. 1978 Dec;15(4):1277–1286. doi: 10.1016/0092-8674(78)90053-3. [DOI] [PubMed] [Google Scholar]
- Kluger M. J., Ringler D. H., Anver M. R. Fever and survival. Science. 1975 Apr 11;188(4184):166–168. [PubMed] [Google Scholar]
- Kluger M. J., Vaughn L. K. Fever and survival in rabbits infected with Pasteurella multocida. J Physiol. 1978 Sep;282:243–251. doi: 10.1113/jphysiol.1978.sp012460. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Manzella J. P., Roberts N. J., Jr Human macrophage and lymphocyte responses to mitogen stimulation after exposure to influenza virus, ascorbic acid, and hyperthermia. J Immunol. 1979 Nov;123(5):1940–1944. [PubMed] [Google Scholar]
- Miller M. J., Xuong N. H., Geiduschek E. P. A response of protein synthesis to temperature shift in the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5222–5225. doi: 10.1073/pnas.76.10.5222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murphy P. A., Simon P. L., Willoughby W. F. Endogenous pyrogens made by rabbit peritoneal exudate cells are identical with lymphocyte-activating factors made by rabbit alveolar macrophages. J Immunol. 1980 May;124(5):2498–2501. [PubMed] [Google Scholar]
- Roberts N. J., Jr, Steigbigel R. T. Effect of in vitro virus infection on response of human monocytes and lymphocytes to mitogen stimulation. J Immunol. 1978 Sep;121(3):1052–1058. [PubMed] [Google Scholar]
- Rosenwasser L. J., Dinarello C. A., Rosenthal A. S. Adherent cell function in murine T-lymphocyte antigen recognition. IV. Enhancement of murine T-cell antigen recognition by human leukocytic pyrogen. J Exp Med. 1979 Sep 19;150(3):709–714. doi: 10.1084/jem.150.3.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ryser J. E., Cerottini J. C., Brunner K. T. Generation of cytolytic T lymphocytes in vitro. IX. induction of secondary CTL responses in primary long-term MLC by supernatants from secondary MLC. J Immunol. 1978 Feb;120(2):370–377. [PubMed] [Google Scholar]
- Tissières A., Mitchell H. K., Tracy U. M. Protein synthesis in salivary glands of Drosophila melanogaster: relation to chromosome puffs. J Mol Biol. 1974 Apr 15;84(3):389–398. doi: 10.1016/0022-2836(74)90447-1. [DOI] [PubMed] [Google Scholar]
- Vaughn L. K., Bernheim H. A., Kluger M. J. Fever in the lizard Dipsosaurus dorsalis. Nature. 1974 Dec 6;252(5483):473–474. doi: 10.1038/252473a0. [DOI] [PubMed] [Google Scholar]
- Wang C., Gomer R. H., Lazarides E. Heat shock proteins are methylated in avian and mammalian cells. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3531–3535. doi: 10.1073/pnas.78.6.3531. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamauchi K., Murphy D., Cantor H., Gershon R. K. Analysis of an antigen-specific H-2-restricted cell-free products(s) made by "I-J-" Ly-2 cells (Ly-2 TsF) that suppresses Ly-2 cell-depleted spleen cell activity. Eur J Immunol. 1981 Nov;11(11):913–918. doi: 10.1002/eji.1830111111. [DOI] [PubMed] [Google Scholar]