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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1976 Mar;23(3):414–428.

Reconstitution of defective cellular immunity with foetal thymus and dialysable transfer factor. Long-term studies in a patient with chronic mucocutaneous candidiasis.

C H Kirkpatrick, E A Ottenson, T K Smith, S A Wells, J F Burdick
PMCID: PMC1538390  PMID: 947642

Abstract

Extensive studies of a 9-year-old boy with recurrent pulmonary infections and chronic mucocutaneous candidiasis disclosed a severe defect in cell-mediated immunity but normal humoral immune responses. These immunological defects were not improved by initial treatment with transfer factor. After receiving a foetal thymus transplant the patient developed positive delayed-type skin tests, could be sensitized with chlorodinitrobenzene, and showed progressive improvement of in vitro lymphocyte functions including spontaneous formation of rosettes with sheep erythrocytes and positive responses to phytohaemagglutinin, concanavalin A and allogeneic leucocytes. Moreover, lymph node cellularity increased, especially in the thymus-dependent zones. Though the in vitro responses persisted for over 1 year, skin tests became unreactive at 38 weeks. However, in contrast to the pre-transplant experience transfer factor was now effective in inducing positive skin tests. These studies provide a chronological account of the effect of the thymus on expression of lymphocyte-mediated immune responses in man and suggest that thymus-derived cells are required for acquisition of transfer factor-induced cellular immunity.

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Selected References

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  1. Ammann A. J., Wara D. W., Salmon S., Perkins H. Thymus transplantation. Permanent reconstitution of cellular immunity in a patient with sex-linked combined immunodeficiency. N Engl J Med. 1973 Jul 5;289(1):5–9. doi: 10.1056/NEJM197307052890102. [DOI] [PubMed] [Google Scholar]
  2. August C. S., Berkel A. I., Levey R. H., Rosen F. S., Kay H. E. Establishment of immunological competence in a child with congenital thymic aplasia by a graft of fetal thymus. Lancet. 1970 May 23;1(7656):1080–1083. doi: 10.1016/s0140-6736(70)92755-8. [DOI] [PubMed] [Google Scholar]
  3. Bach F. H., Voynow N. K. One-way stimulation in mixed leukocyte cultures. Science. 1966 Jul 29;153(3735):545–547. doi: 10.1126/science.153.3735.545. [DOI] [PubMed] [Google Scholar]
  4. Biggar W. D., Stutman O., Good R. A. Morphological and functional studies of fetal thymus transplants in mice. J Exp Med. 1972 Apr 1;135(4):793–807. doi: 10.1084/jem.135.4.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blaese R. M., Weiden P., Oppenheim J. J., Waldmann T. A. Phytohemagglutinin as a skin test for the evaluation of cellular immune competence in man. J Lab Clin Med. 1973 Apr;81(4):538–548. [PubMed] [Google Scholar]
  6. Buckley R. H., Amos D. B., Kremer W. B., Stickel D. L. Incompatible bone-marrow transplantation in lymphopenic immunologic deficiency. Circumvention of fatal graft-versus-host disease by immunologic enhancement. N Engl J Med. 1971 Nov 4;285(19):1035–1042. doi: 10.1056/NEJM197111042851901. [DOI] [PubMed] [Google Scholar]
  7. Byrd W. J., Von Boehmer H., Rouse B. T. The role of the thymus in maturational development of phytohemagglutinin and pokeweed mitogen responsiveness. Cell Immunol. 1973 Jan;6(1):12–24. doi: 10.1016/0008-8749(73)90002-6. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Cleveland W. W. Immunologic reconstitution in the DiGeorge syndrome by fetal thymic transplant. Birth Defects Orig Artic Ser. 1975;11(1):352–356. [PubMed] [Google Scholar]
  10. Cooper M. D., Raymond D. A., Peterson R. D., South M. A., Good R. A. The functions of the thymus system and the bursa system in the chicken. J Exp Med. 1966 Jan 1;123(1):75–102. doi: 10.1084/jem.123.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gallin J. I., Kirkpatrick C. H. Chemotactic activity in dialyzable transfer factor. Proc Natl Acad Sci U S A. 1974 Feb;71(2):498–502. doi: 10.1073/pnas.71.2.498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gatti R. A., Gershanik J. J., Levkoff A. H., Wertelecki W., Good R. A. DiGeorge syndrome associated with combined immunodeficiency. Dissociation of phytohemagglutinin and mixed leukocyte culture responses. J Pediatr. 1972 Nov;81(5):920–926. doi: 10.1016/s0022-3476(72)80544-4. [DOI] [PubMed] [Google Scholar]
  13. Gershon R. K. T cell control of antibody production. Contemp Top Immunobiol. 1974;3:1–40. doi: 10.1007/978-1-4684-3045-5_1. [DOI] [PubMed] [Google Scholar]
  14. Githens J. H., Fulginiti V. A., Suvatte V., Schroter G., Hathaway W. E., Pearlman D. S., Kay H. E., Terasaki P. I., Hill G. J., Kempe C. H. Grafting of fetal thymus and hematopoietic tissue in infants with immune deficiency syndromes. Transplantation. 1973 May;15(5):427–434. [PubMed] [Google Scholar]
  15. HITZIG W. H., KAY H. E., COTTIER H. FAMILIAL LYMPHOPENIA WITH AGAMMAGLOBULINEMIA: AN ATTEMPT AT TREATMENT BY IMPLANTATION OF FETAL THYMUS. Lancet. 1965 Jul 24;2(7404):151–154. doi: 10.1016/s0140-6736(65)90231-x. [DOI] [PubMed] [Google Scholar]
  16. Hong R., Cooper M. D., Allan M. J., Kay H. E., Meuwissen H., Good R. A. Immunological restitution in lymphopenic immunological deficiency syndrome. Lancet. 1968 Mar 9;1(7541):503–506. doi: 10.1016/s0140-6736(68)91468-2. [DOI] [PubMed] [Google Scholar]
  17. Janossy G., Greaves M. F. Lymphocyte activation. I. Response of T and B lymphocytes to phytomitogens. Clin Exp Immunol. 1971 Oct;9(4):483–498. [PMC free article] [PubMed] [Google Scholar]
  18. Jondal M., Holm G., Wigzell H. Surface markers on human T and B lymphocytes. I. A large population of lymphocytes forming nonimmune rosettes with sheep red blood cells. J Exp Med. 1972 Aug 1;136(2):207–215. doi: 10.1084/jem.136.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Katz D. H., Benacerraf B. The regulatory influence of activated T cells on B cell responses to antigen. Adv Immunol. 1972;15:1–94. doi: 10.1016/s0065-2776(08)60683-5. [DOI] [PubMed] [Google Scholar]
  20. Kirkpatrick C. H., Rich R. R., Smith T. K. Effect of transfer factor on lymphocyte function in anergic patients. J Clin Invest. 1972 Nov;51(11):2948–2958. doi: 10.1172/JCI107119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lawrence H. S., Zweiman B. Transfer factor deficiency response--a mechanism of anergy in Boeck's sarcoid. Trans Assoc Am Physicians. 1968;81:240–248. [PubMed] [Google Scholar]
  22. Levy R. L., Bach M. L., Huang S., Bach F. H., Hong R., Ammann A. J., Bortin M., Kay H. E. Thymic transplantation in a case of chronic mucocutaneous candidiasis. Lancet. 1971 Oct 23;2(7730):898–900. doi: 10.1016/s0140-6736(71)92503-7. [DOI] [PubMed] [Google Scholar]
  23. Marcolongo R., Di Paolo N. Fetal thymic transplant in patients with Hodgkin's disease. Blood. 1973 May;41(5):625–633. [PubMed] [Google Scholar]
  24. OSOBA D., MILLER J. F. THE LYMPHOD TISSUES AND IMMUNE RESPONSES OF NEONATALLY THYMECTOMIZED MICE BEARING THYMUS TISSUE IN MILLIPORE DIFFUSION CHAMBERS. J Exp Med. 1964 Jan 1;119:177–194. doi: 10.1084/jem.119.1.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Okumura K., Tada T. Regulation of homocytotropic antibody formation in the rat. VI. Inhibitory effect of thymocytes on the homocytotropic antibody response. J Immunol. 1971 Dec;107(6):1682–1689. [PubMed] [Google Scholar]
  26. Pachman L. M., Kirkpatrick C. H., Kaufman D. H., Rothberg R. M. The lack of effect of transfer factor in thymic dysplasia with immunoglobulin synthesis. J Pediatr. 1974 May;84(5):681–688. doi: 10.1016/s0022-3476(74)80009-0. [DOI] [PubMed] [Google Scholar]
  27. Pantelouris E. M. Observations on the immunobiology of 'nude' mice. Immunology. 1971 Feb;20(2):247–252. [PMC free article] [PubMed] [Google Scholar]
  28. Pritchard H., Micklem H. S. Immune responses in congenitally thymus-less mice. I. Absence of response to oxazolone. Clin Exp Immunol. 1972 Jan;10(1):151–161. [PMC free article] [PubMed] [Google Scholar]
  29. Pritchard H., Riddaway J., Micklem H. S. Immune responses in congenitally thymus-less mice. II. Quantitative studies of serum immunoglobulins, the antibody response to sheep erythrocytes, and the effect of thymus allografting. Clin Exp Immunol. 1973 Jan;13(1):125–138. [PMC free article] [PubMed] [Google Scholar]
  30. Rocklin R. E., Meyers O. L., David J. R. An in vitro assay for cellular hypersensitivity in man. J Immunol. 1970 Jan;104(1):95–102. [PubMed] [Google Scholar]
  31. Rádl J., Dooren L. J., Eijsvoogel V. P., van Went J. J., Hijmans W. An immunological study during post-transplantation follow-up of a case of severe combined immunodeficiency. Clin Exp Immunol. 1972 Feb;10(2):367–382. [PMC free article] [PubMed] [Google Scholar]
  32. St Geme J. W., Jr, Wanker J. J., Jr, Arce M. A., Van Pelt L. F. The effect of repeated mumps skin tests on the induction of antibody. Pediatrics. 1971 Sep;48(3):445–447. [PubMed] [Google Scholar]
  33. Steele R. W., Limas C., Thurman G. B., Schuelein M., Bauer H., Bellanti J. A. Familial thymic aplasia. Attempted reconstitution with fetal thymus in a Millipore diffusion chamber. N Engl J Med. 1972 Oct 19;287(16):787–791. doi: 10.1056/NEJM197210192871602. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. WINNER H. I. A study of Candida albicans agglutinins in human sera. J Hyg (Lond) 1955 Dec;53(4):509–512. doi: 10.1017/s0022172400001005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wells S. A., Burdick J. F., Ketcham A. S., Christiansen C. Transplantation of the parathyroid glands in dogs. Biochemical, histological, and radioimmunoassay proof of function. Transplantation. 1973 Jan;15(1):179–182. doi: 10.1097/00007890-197301000-00027. [DOI] [PubMed] [Google Scholar]
  37. Wortis H. H., Nehlsen S., Owen J. J. Abnormal development of the thymus in "nude" mice. J Exp Med. 1971 Sep 1;134(3 Pt 1):681–692. doi: 10.1084/jem.134.3.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. van Bekkum D. W. Use and abuse of hemopoietic cell grafts in immune deficiency diseases. Transplant Rev. 1972;9:3–53. doi: 10.1111/j.1600-065x.1972.tb01560.x. [DOI] [PubMed] [Google Scholar]

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