Abstract
Cell-mediated and humoral immune responses of mutant diabetic db+/db+ mice were evaluated using in vivo and in vitro immunological assays. When compared to lean, nondiabetic db+/m+ or m+/m+ mice, db+/db+ mice demonstrated markedly altered in vivo immune responses characterized by a significantly diminished ability to reject allogeneic skin grafts, a markedly diminished capacity to generate cytotoxic cells after sensitization with allogeneic EL-4 lymphoma cells and a significantly enhanced plaque-forming cell response to sheep erythrocytes. In contrast, spleen cells from db+/db+ mice demonstrated only minimal alterations in in vitro responses to mitogens and allogeneic cells and no alteration in their capacity to generate an in vitro plaque-forming cell response. The spleens and thymuses of db+/db+ mice weighed significantly less than organs from db+/db+ mice. In addition, thymuses from db+/db+ mice demonstrated a marked deficiency in in vivo [125I]UdR uptake. These data suggest that the altered metabolic status of the diabetic host influences immune function in vivo possibly due to abnormal function of lymphocyte subpopulations.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bagdade J. D., Root R. K., Bulger R. J. Impaired leukocyte function in patients with poorly controlled diabetes. Diabetes. 1974 Jan;23(1):9–15. doi: 10.2337/diab.23.1.9. [DOI] [PubMed] [Google Scholar]
- Barthold D. R., Kysela S., Steinberg A. D. Decline in suppressor T cell function with age in female NZB mice. J Immunol. 1974 Jan;112(1):9–16. [PubMed] [Google Scholar]
- Boyle W. An extension of the 51Cr-release assay for the estimation of mouse cytotoxins. Transplantation. 1968 Sep;6(6):761–764. doi: 10.1097/00007890-196809000-00002. [DOI] [PubMed] [Google Scholar]
- Brody J. I., Merlie K. Metabolic and biosynthetic features of lymphocytes from patients with diabetes mellitus: similarities to lymphocytes in chronic lymphocytic leukaemia. Br J Haematol. 1970 Aug;19(2):193–201. doi: 10.1111/j.1365-2141.1970.tb01616.x. [DOI] [PubMed] [Google Scholar]
- Bullock W. W., Möller E. "Spontaneous" B cell activation due to loss of normal mouse serum suppressor. Eur J Immunol. 1972 Dec;2(6):514–517. doi: 10.1002/eji.1830020609. [DOI] [PubMed] [Google Scholar]
- Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chick W. L., Like A. A. Studies in the diabetic mutant mouse. IV. DBM, a modified diabetic mutant produced by outcrossing of the original strain. Diabetologia. 1970 Jun;6(3):252–256. doi: 10.1007/BF01212234. [DOI] [PubMed] [Google Scholar]
- Drachman R. H., Root R. K., Wood W. B., Jr Studies on the effect of experimental nonketotic diabetes mellitus on antibacterial defense. I. Demonstration of a defect in phagocytosis. J Exp Med. 1966 Aug 1;124(2):227–240. doi: 10.1084/jem.124.2.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fathman C. G., Handwerger B. S., Sachs D. H. Evidence for a role of Ir-associated alloantigens in mixed lymphocyte culture stimulation. J Exp Med. 1974 Sep 1;140(3):853–858. doi: 10.1084/jem.140.3.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fernandes G., Halberg F., Yunis E. J., Good R. A. Circadian rhythmic plaque-forming cell response of spleens from mice immunized with SRBC. J Immunol. 1976 Sep;117(3):962–966. [PubMed] [Google Scholar]
- Fernandes G., Yunis E. J., Good R. A. Depression of cytotoxic T cell subpopulation in mice by hydrocortisone treatment. Clin Immunol Immunopathol. 1975 Jul;4(2):304–313. doi: 10.1016/0090-1229(75)90066-5. [DOI] [PubMed] [Google Scholar]
- Fernandes G., Yunis E. J., Good R. A. Influence of protein restriction on immune functions in NZB mice. J Immunol. 1976 Mar;116(3):782–790. [PubMed] [Google Scholar]
- Gershon R. K. A disquisition on suppressor T cells. Transplant Rev. 1975;26:170–185. doi: 10.1111/j.1600-065x.1975.tb00179.x. [DOI] [PubMed] [Google Scholar]
- Handwerger B. S., Koren H. S. The nature of the effector cell in antibody-dependent, cell-mediated cytolysis (ADCC): the cytotoxic activity of murine tumor cells and peritoneal macrophages. Clin Immunol Immunopathol. 1976 Mar;5(2):272–281. doi: 10.1016/0090-1229(76)90032-5. [DOI] [PubMed] [Google Scholar]
- Helderman J. H., Strom T. B. Emergence of insulin receptors upon alloimmune T cells in the rat. J Clin Invest. 1977 Feb;59(2):338–344. doi: 10.1172/JCI108646. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hill H. R., Sauls H. S., Dettloff J. L., Quie P. G. Impaired leukotactic responsiveness in patients with juvenile diabetes mellitus. Clin Immunol Immunopathol. 1974 Apr;2(3):395–403. doi: 10.1016/0090-1229(74)90057-9. [DOI] [PubMed] [Google Scholar]
- Hodes R. J., Handwerger B. S., Terry W. D. Synergy between subpopulations of mouse spleen cells in the in vitro generation of cell-mediated cytotoxicity: evidence for the involvement of a non-T cell. J Exp Med. 1974 Dec 1;140(6):1646–1659. doi: 10.1084/jem.140.6.1646. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hummel K. P., Dickie M. M., Coleman D. L. Diabetes, a new mutation in the mouse. Science. 1966 Sep 2;153(3740):1127–1128. doi: 10.1126/science.153.3740.1127. [DOI] [PubMed] [Google Scholar]
- MARKS V. An improved glucose-oxidase method for determining blood, C.S.F. and urine glucose levels. Clin Chim Acta. 1959 May;4(3):395–400. doi: 10.1016/0009-8981(59)90110-x. [DOI] [PubMed] [Google Scholar]
- MARTINEZ C., SMITH J. M., AUST J. B., GOOD R. A. Acquired tolerance to skin homografts in mice of different strains. Proc Soc Exp Biol Med. 1958 Apr;97(4):736–738. doi: 10.3181/00379727-97-23863. [DOI] [PubMed] [Google Scholar]
- MacCuish A. C., Jordan J., Campbell C. J., Duncan L. J., Irvine W. J. Cell-mediated immunity in diabetes mellitus; lymphocyte transformation by insulin and insulin fragments in insulin-treated and newly-diagnosed diabetes. Diabetes. 1975 Jan;24(1):36–43. doi: 10.2337/diab.24.1.36. [DOI] [PubMed] [Google Scholar]
- MacCuish A. C., Urbaniak S. J., Campbell C. J., Duncan L. J., Irvine W. J. Phytohemagglutinin transformation and circulating lymphocyte subpopulations in insulin-dependent diabetic patients. Diabetes. 1974 Aug;23(8):708–712. doi: 10.2337/diab.23.8.708. [DOI] [PubMed] [Google Scholar]
- Mahmoud A. A., Rodman H. M., Mandel M. A., Warren K. S. Induced and spontaneous diabetes mellitus and suppression of cell-mediated immunologic responses. Granuloma formation, delayed dermal reactivity and allograft rejection. J Clin Invest. 1976 Feb;57(2):362–367. doi: 10.1172/JCI108287. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCarthy M. M., Dutton R. W. The humoral response of mouse spleen cells to two types of sheep erythrocytes. I. Genetic control of the response to H and L SRBC. J Immunol. 1975 Nov;115(5):1316–1321. [PubMed] [Google Scholar]
- Pallavicini M. G., Nichols W. K. Inhibition of lymphocyte blastogenesis by factor(s) in alloxan-diabetic rat plasma. Diabetes. 1976 Jul;25(7):614–622. doi: 10.2337/diab.25.7.614. [DOI] [PubMed] [Google Scholar]
- Schwartz R. H., Bianco A. R., Handwerger B. S., Kahn C. R. Demonstration that monocytes rather than lymphocytes are the insulin-binding cells in preparations of humah peripheral blood mononuclear leukocytes: implications for studies of insulin-resistant states in man. Proc Natl Acad Sci U S A. 1975 Feb;72(2):474–478. doi: 10.1073/pnas.72.2.474. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soli A. H., Kahn C. R., Neville D. M., Jr, Roth J. Insulin receptor deficiency in genetic and acquired obesity. J Clin Invest. 1975 Oct;56(4):769–780. doi: 10.1172/JCI108155. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strom T. B., Bear R. A., Carpenter C. B. Insulin-induced augmentation of lymphocyte-mediated cytotoxicity. Science. 1975 Mar 28;187(4182):1206–1208. doi: 10.1126/science.163492. [DOI] [PubMed] [Google Scholar]
- THOMPSON G. E., DEFALCO R. J. ALLOXAN AND HYPERSENSITIVITY. II. EFFECT OF ALLOXAN ON HYPERSENSITIVITY REACTIONS IN THE MOUSE, RAT, AND GUINEA PIG. Cornell Vet. 1965 Jan;55:66–74. [PubMed] [Google Scholar]
- Taylor W. G. "Feeding the baby"--serum and other supplements to chemically defined medium. J Natl Cancer Inst. 1974 Nov;53(5):1449–1457. doi: 10.1093/jnci/53.5.1449. [DOI] [PubMed] [Google Scholar]
- Thompson G. E. Enhancing effect of insulin on the tuberculin reaction in the albino rat. Nature. 1967 Aug 12;215(5102):748–749. doi: 10.1038/215748a0. [DOI] [PubMed] [Google Scholar]
- Waymouth C. "Feeding the baby"--designing the culture milieu to enhance cell stability. J Natl Cancer Inst. 1974 Nov;53(5):1443–1448. doi: 10.1093/jnci/53.5.1443. [DOI] [PubMed] [Google Scholar]
- Webb S. R., Loria R. M., Madge G. E., Kibrick S. Susceptibility of mice to group B coxsackie virus is influenced by the diabetic gene. J Exp Med. 1976 May 1;143(5):1239–1248. doi: 10.1084/jem.143.5.1239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zatz M. M., Goldstein A. L. Antigen-induced depression of DNA synthesis in mouse spleen. J Immunol. 1973 May;110(5):1312–1317. [PubMed] [Google Scholar]