Abstract
Experiments have been carried out to investigate the possible role of the sensitized lymphocyte in mediating the fevers of delayed hypersensitivity. Rabbits were made delayed hypersensitive to one of several heterologous proteins (bovine gamma globulin, bovine serum albumin, or human serum albumin) by footpad injection of antigen or antigen conjugated with dinitrophenol and incorporated in complete Freund's adjuvant. At intervals after sensitization, various tissues were removed, and single cell suspensions were incubated overnight with either carrier protein or conjugate in vitro. Release of an endogenous pyrogen (EP) was assayed by intravenous injection of the supernatant fluid into unsensitized rabbits. Of the tissues tested only those containing both lymphocytes and pyrogen-producing cells, blood, spleen, and draining lymph nodes, released detectable amounts of EP when incubated with antigen in vitro. Incubation of normal blood cells with specifically sensitized lymphocytes and antigen also resulted in significant release of pyrogen. Similarly, blood leukocytes released EP in vitro after mixture with supernates derived from incubation of sensitized lymphocytes and antigen. Cells and supernatant fluids from draining lymph nodes were usually effective in activating normal blood leukocytes earlier after sensitization than were those from mesenteric lymph nodes, suggesting that such cells, or antigen, had migrated from the original site of sensitization. The activator was soluble, nonpyrogenic in the dosages tested, and required incubation of viable cells with specific antigen for its production. These properties suggest that it may belong to the class of "lymphokines," biologically active agents released from lymphocytes that have been activated by immunologic or certain nonimmunologic stimuli.
Full Text
The Full Text of this article is available as a PDF (1.0 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ATKINS E., HEIJN C., Jr STUDIES ON TUBERCULIN FEVER. 3. MECHANISMS INVOLVED IN THE RELEASE OF ENDOGENOUS PYROGEN IN VITRO. J Exp Med. 1965 Aug 1;122:207–235. doi: 10.1084/jem.122.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ATKINS E. STUDIES IN STAPHYLOCOCCAL FEVER. II. RESPONSES TO CULTURE FILTRATES. Yale J Biol Med. 1963 Jun;35:472–488. [PMC free article] [PubMed] [Google Scholar]
- Atkins E., Bodel P., Francis L. Release of an endogenous pyrogen in vitro from rabbit mononuclear cells. J Exp Med. 1967 Aug 1;126(2):357–384. doi: 10.1084/jem.126.2.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bodel P., Dillard M. Studies on steroid fever: I. Production of leukocyte pyrogen in vitro by etiocholanolone. J Clin Invest. 1968 Jan;47(1):107–117. doi: 10.1172/JCI105701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen S., Vassalli P., Benacerraf B., McCluskey R. T. The distribution of antigenic and nonantigenic compounds within draining lymph nodes. Lab Invest. 1966 Jul;15(7):1143–1155. [PubMed] [Google Scholar]
- Dinarello C. A., Bodel P. T., Atkins E. The role of the liver in the production of fever and in pyrogenic tolerance. Trans Assoc Am Physicians. 1968;81:334–344. [PubMed] [Google Scholar]
- EISEN H. N., KERN M., NEWTON W. T., HELMREICH E. A study of the distribution of 2,4-dinitrobenzene sensitizers between isolated lymph node cells and extracellular medium in relation to induction of contact skin sensitivity. J Exp Med. 1959 Aug 1;110(2):187–206. doi: 10.1084/jem.110.2.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GREY H. M., BRIGGS W., FARR R. S. The passive transfer of sensitivity to antigen-induced fever. J Clin Invest. 1961 Apr;40:703–706. doi: 10.1172/JCI104303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HALL C. H., Jr, ATKINS E. Studies on tuberculin fever. I. The mechanism of fever in tuberculin hypersensitivity. J Exp Med. 1959 Apr 1;109(4):339–359. doi: 10.1084/jem.109.4.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Han S. S., Han I. H., Johnson A. G. The fate of isologous, homologous and heterologous ferritin molecules in the rat. Am J Anat. 1970 Oct;129(2):141–167. doi: 10.1002/aja.1001290203. [DOI] [PubMed] [Google Scholar]
- Harris T. N., Ehrich W. E. THE FATE OF INJECTED PARTICULATE ANTIGENS IN RELATION TO THE FORMATION OF ANTIBODIES. J Exp Med. 1946 Jul 31;84(2):157–165. [PMC free article] [PubMed] [Google Scholar]
- Lind P. E. Cellular localization of 125I-labelled Salmonella adelaide flagellin following injection into the rat in the presence of Freund's complete adjuvant. Aust J Exp Biol Med Sci. 1968 Apr;46(2):189–208. doi: 10.1038/icb.1968.16. [DOI] [PubMed] [Google Scholar]
- Moore D. M., Cheuk S. F., Morton J. D., Berlin R. D., Wood W. B., Jr Studies on the pathogenesis of fever. 18. Activation of leukocytes for pyrogen production. J Exp Med. 1970 Jan 1;131(1):179–188. doi: 10.1084/jem.131.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Root R. K., Wolff S. M. Pathogenetic mechanisms in experimental immune fever. J Exp Med. 1968 Aug 1;128(2):309–323. doi: 10.1084/jem.128.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- TALMAGE D. W., MAURER P. H. I131-Labelled antigen precipitation as a measure of quantity and quality of antibody. J Infect Dis. 1953 May-Jun;92(3):288–300. doi: 10.1093/infdis/92.3.288. [DOI] [PubMed] [Google Scholar]
- UHR J. W., BRANDRISS M. W. Delayed hypersensitivity. IV. Systemic reactivity of guinea pigs sensitized to protein antigens. J Exp Med. 1958 Dec 1;108(6):905–924. doi: 10.1084/jem.108.6.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
- UHR J. W., SCHARFF M. Delayed hypersensitivity. V. The effect of x-irradiation on the development of delayed hypersensitivity and antibody formation. J Exp Med. 1960 Jul 1;112:65–76. doi: 10.1084/jem.112.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]