Abstract
The immune functions of neonatally thymectomized C3Hf mice exposed only temporarily to thymus function show a progressive decay with time in the absence of the thymus. The immune responses studied at different ages in the range of 100–600 days were: first-set rejection of H-2-compatible and incompatible skin allografts, second-set rejection of skin allografts, capacity of spleen cells to produce graft-versus-host reactions in F1 hybrids, resistance to infection with mouse hepatitis virus, and response of spleen cells to phytohemagglutinin in vitro. These long-term studies had the purpose of determining the duration of the restoration induced by thymus function when the mice were exposed only temporarily to it. Different models were used but the two basic ones were: (a) mice grafted intraperitoneally at 15 days of age with a syngeneic thymus that was removed surgically at 10, 20, or 30 days after grafting, and (b) mice grafted at 15 days of age with allogeneic strain A thymoma or C57BL thymus, these representing situations in which there is spontaneous rejection of the restoring graft. In all the experimental models used, the animals were restored when tested at 100 days of age, but progressively became immunologically incapacitated at 200–300 days of age. From the more controlled experiments in which the restoring thymus graft was removed surgically, the following conclusions can be drawn. (a) A short exposure to a thymus graft can produce restoration of immune functions in neonatally thymectomized mice, but this restoration is not self-sustaining in the absence of the thymus and declines progressively with age. The decline usually starts at 200–300 days of age. (b) This was especially clear in experiments in which the same animal was tested twice in its lifetime for capacity to produce graft-versus-host reactions; these animals were competent at 100 days and became incompetent at 400 days of age. (c) The shortest period of thymic exposure studied was 10 days; if vascularization of the graft is taken into account, 2–3 days of thymic function are sufficient to produce restoration. (d) The immune decay observed in the thymectomized animals exposed temporarily to thymus was more profound than the physiological decay of immunity observed in control animals of similar age. (e) Of all the tests studied, the response of spleen cells to phytohemagglutinin was to be preserved the longest in animals exposed only temporarily to thymic function. The present results were interpreted in accordance with our previous findings indicating that a population of postthymic cells can be developed by temporary exposure of neonatally thymectomized animals to thymic function, but that this population is not self-sustaining in the absence of thymus and progressively decays by physiological attrition.
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Selected References
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- August C. S., Rosen F. S., Filler R. M., Janeway C. A., Markowski B., Kay H. E. Implantation of a foetal thymus, restoring immunological competence in a patient with thymic aplasia (Digeorge's syndrome). Lancet. 1968 Dec 7;2(7580):1210–1211. doi: 10.1016/s0140-6736(68)91693-0. [DOI] [PubMed] [Google Scholar]
- Cleveland W. W., Fogel B. J., Brown W. T., Kay H. E. Foetal thymic transplant in a case of Digeorge's syndrome. Lancet. 1968 Dec 7;2(7580):1211–1214. doi: 10.1016/s0140-6736(68)91694-2. [DOI] [PubMed] [Google Scholar]
- DALMASSO A. P., MARTINEZ C., SJODIN K., GOOD R. A. STUDIES ON THE ROLE OF THE THYMUS IN IMMUNOBIOLOGY; RECONSTITUTION OF IMMUNOLOGIC CAPACITY IN MICE THYMECTOMIZED AT BIRTH. J Exp Med. 1963 Dec 1;118:1089–1109. doi: 10.1084/jem.118.6.1089. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis W. E., Jr, Cole L. J. Homograft response in adult-thymectomized mice: deficiency with aging and after low dose-rate gamma-irradiation. Exp Gerontol. 1968 Mar;3(1):9–17. doi: 10.1016/0531-5565(68)90051-x. [DOI] [PubMed] [Google Scholar]
- Dukor P., Miller J. F., House W., Allman V. Regeneration of thymus grafts. I. Histological and cytological aspects. Transplantation. 1965 Sep;3(5):639–668. doi: 10.1097/00007890-196509000-00006. [DOI] [PubMed] [Google Scholar]
- Dupuy J. M., Perey D. Y., Good R. A. Transfer of skin homograft immunity with a plasma factor. J Immunol. 1970 Jun;104(6):1523–1529. [PubMed] [Google Scholar]
- EAST J., PARROTT D. M., CHESTERMAN F. C., POMERANCE A. THE APPEARANCE OF A HEPATOTROPHIC VIRUS IN MICE THYMECTOMIZED AT BIRTH. J Exp Med. 1963 Dec 1;118:1069–1082. doi: 10.1084/jem.118.6.1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gallily R., Warwick A., Bang F. B. Ontogeny of macrophage resistance to mouse hepatitis in vivo and in vitro. J Exp Med. 1967 Apr 1;125(4):537–548. doi: 10.1084/jem.125.4.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LEUCHARS E., CROSS A. M., DUKOR P. THE RESTORATION OF IMMUNOLOGICAL FUNCTION BY THYMUS GRAFTING IN THYMECTOMIZED IRRADIATED MICE. Transplantation. 1965 Jan;3:28–38. doi: 10.1097/00007890-196501000-00004. [DOI] [PubMed] [Google Scholar]
- Metcalf D. Delayed effect of thymectomy in adult life on immunological competence. Nature. 1965 Dec 25;208(5017):1336–1336. doi: 10.1038/2081336a0. [DOI] [PubMed] [Google Scholar]
- Miller J. F. Effect of thymectomy in adult mice on immunological responsiveness. Nature. 1965 Dec 25;208(5017):1337–1338. doi: 10.1038/2081337a0. [DOI] [PubMed] [Google Scholar]
- Monaco A. P., Wood M. L., Russell P. S. Adult Thymectomy: Effect on Recovery from Immunologic Depression in Mice. Science. 1965 Jul 23;149(3682):432–435. doi: 10.1126/science.149.3682.432. [DOI] [PubMed] [Google Scholar]
- Stutman O., Good R. A. Immunocompetence of embryonic hemopoietic cells after traffic to thymus. Transplant Proc. 1971 Mar;3(1):923–925. [PubMed] [Google Scholar]
- Stutman O., Yunis E. J., Good R. A. Carcinogen-induced tumors of the thymus. 3. Restoration of neonatally thymectomized mice with thymomas in cell-impermeable chambers. J Natl Cancer Inst. 1969 Aug;43(2):499–508. [PubMed] [Google Scholar]
- Stutman O., Yunis E. J., Good R. A. Carcinogen-induced tumors of the thymus. I. Restoration of neonatally thymectomized mice with a functional thymoma. J Natl Cancer Inst. 1968 Dec;41(6):1431–1452. [PubMed] [Google Scholar]
- Stutman O., Yunis E. J., Good R. A. Carcinogen-induced tumors of the thymus. IV. Humoral influences of normal thymus and functional thymomas and influence of posthymectomy period on restoration. J Exp Med. 1969 Oct 1;130(4):809–819. doi: 10.1084/jem.130.4.809. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stutman O., Yunis E. J., Good R. A. Studies on thymus function. I. Cooperative effect of thymic function and lymphohemopoietic cells in restoration of neonatally thymectomized mice. J Exp Med. 1970 Sep 1;132(3):583–600. doi: 10.1084/jem.132.3.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stutman O., Yunis E. J., Good R. A. Studies on thymus function. II. Cooperative effect of newborn and embryonic hemopoietic liver cells with thymus function. J Exp Med. 1970 Sep 1;132(3):601–612. doi: 10.1084/jem.132.3.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stutman O., Yunis E. J., Martinez C., Good R. A. Reversal of post-thymectomy wasting disease in mice by multiple thymus grafts. J Immunol. 1967 Jan;98(1):79–87. [PubMed] [Google Scholar]
- Taylor R. B. Decay of immunological responsiveness after thymectomy in adult life. Nature. 1965 Dec 25;208(5017):1334–1335. doi: 10.1038/2081334a0. [DOI] [PubMed] [Google Scholar]
- YUNIS E. J., HILGARD H. R., MARTINEZ C., GOOD R. A. STUDIES ON IMMUNOLOGIC RECONSTITUTION OF THYMECTOMIZED MICE. J Exp Med. 1965 Apr 1;121:607–632. doi: 10.1084/jem.121.4.607. [DOI] [PMC free article] [PubMed] [Google Scholar]