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The American Journal of Pathology logoLink to The American Journal of Pathology
. 1994 Aug;145(2):281–286.

Transplantation of T cell-mediated, lymphoreticular disease from the scurfy (sf) mouse.

V L Godfrey 1, B T Rouse 1, J E Wilkinson 1
PMCID: PMC1887402  PMID: 8053488

Abstract

The X-linked mutation, scurfy (sf), causes a fatal lymphoreticular disease characterized by runting, lymphadenopathy, splenomegaly, hypergammaglobulinemia, exfoliative dermatitis, Coombs'-positive anemia, and death by 24 days of age. T lymphocytes are required to mediate this syndrome as shown by a total absence of disease in mice bred to be scurfy and nude (sf/Y; nu/nu). The scurfy phenotype is not transmitted by sf/Y bone marrow transplants, though cells of scurfy origin do reconstitute all lymphoid organs in the recipient mouse. These data suggest that scurfy disease results from an abnormal T cell development process and not from an intrinsic stem cell defect. We therefore tested the ability of transplanted scurfy thymuses to transmit scurfy disease to congenic euthymic mice, to athymic (nude) mice, and to severe combined immunodeficiency (SCID) mice. Euthymic recipients of sf/Y thymic grafts remained clinically normal as did all SCID and nude recipients of normal thymus transplants. Morphological lesions similar to those found in scurfy mice occurred in all H-2-compatible nude and SCID recipients of sf/Y thymic grafts. Intraperitoneal injections of scurfy thymocytes, splenocytes, and lymph node cells also transmitted the scurfy phenotype to H-2-compatible nude mice and SCID mice. Our findings indicate that scurfy disease can be transmitted to T cell-deficient mice by engraftment of scurfy T cells, but that pathogenic scurfy T cell activities can be inhibited (or prevented) in immunocompetent recipient mice.

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Selected References

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  1. Charley M. R., Bangert J. L., Hamilton B. L., Gilliam J. N., Sontheimer R. D. Murine graft-versus-host skin disease: a chronologic and quantitative analysis of two histologic patterns. J Invest Dermatol. 1983 Nov;81(5):412–417. doi: 10.1111/1523-1747.ep12522551. [DOI] [PubMed] [Google Scholar]
  2. Cheng J., Turksen K., Yu Q. C., Schreiber H., Teng M., Fuchs E. Cachexia and graft-vs.-host-disease-type skin changes in keratin promoter-driven TNF alpha transgenic mice. Genes Dev. 1992 Aug;6(8):1444–1456. doi: 10.1101/gad.6.8.1444. [DOI] [PubMed] [Google Scholar]
  3. Eigenbrodt M. L., Eigenbrodt E. H., Thiele D. L. Histologic similarity of murine colonic graft-versus-host disease (GVHD) to human colonic GVHD and inflammatory bowel disease. Am J Pathol. 1990 Nov;137(5):1065–1076. [PMC free article] [PubMed] [Google Scholar]
  4. Ferrara J., Guillen F. J., Sleckman B., Burakoff S. J., Murphy G. F. Cutaneous acute graft-versus-host disease to minor histocompatibility antigens in a murine model: histologic analysis and correlation to clinical disease. J Invest Dermatol. 1986 Apr;86(4):371–375. doi: 10.1111/1523-1747.ep12285612. [DOI] [PubMed] [Google Scholar]
  5. Godfrey V. L., Wilkinson J. E., Rinchik E. M., Russell L. B. Fatal lymphoreticular disease in the scurfy (sf) mouse requires T cells that mature in a sf thymic environment: potential model for thymic education. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5528–5532. doi: 10.1073/pnas.88.13.5528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Godfrey V. L., Wilkinson J. E., Russell L. B. X-linked lymphoreticular disease in the scurfy (sf) mutant mouse. Am J Pathol. 1991 Jun;138(6):1379–1387. [PMC free article] [PubMed] [Google Scholar]
  7. Herron L. R., Eisenberg R. A., Roper E., Kakkanaiah V. N., Cohen P. L., Kotzin B. L. Selection of the T cell receptor repertoire in Lpr mice. J Immunol. 1993 Oct 1;151(7):3450–3459. [PubMed] [Google Scholar]
  8. Matsumoto K., Yoshikai Y., Asano T., Himeno K., Iwasaki A., Nomoto K. Defect in negative selection in lpr donor-derived T cells differentiating in non-lpr host thymus. J Exp Med. 1991 Jan 1;173(1):127–136. doi: 10.1084/jem.173.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Probert L., Keffer J., Corbella P., Cazlaris H., Patsavoudi E., Stephens S., Kaslaris E., Kioussis D., Kollias G. Wasting, ischemia, and lymphoid abnormalities in mice expressing T cell-targeted human tumor necrosis factor transgenes. J Immunol. 1993 Aug 15;151(4):1894–1906. [PubMed] [Google Scholar]
  10. Rich B. E., Campos-Torres J., Tepper R. I., Moreadith R. W., Leder P. Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice. J Exp Med. 1993 Feb 1;177(2):305–316. doi: 10.1084/jem.177.2.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sidman C. L., Marshall J. D., Von Boehmer H. Transgenic T cell receptor interactions in the lymphoproliferative and autoimmune syndromes of lpr and gld mutant mice. Eur J Immunol. 1992 Feb;22(2):499–504. doi: 10.1002/eji.1830220231. [DOI] [PubMed] [Google Scholar]
  12. Suematsu S., Matsuda T., Aozasa K., Akira S., Nakano N., Ohno S., Miyazaki J., Yamamura K., Hirano T., Kishimoto T. IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7547–7551. doi: 10.1073/pnas.86.19.7547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Theofilopoulos A. N., Balderas R. S., Gozes Y., Aguado M. T., Hang L. M., Morrow P. R., Dixon F. J. Association of lpr gene with graft-vs.-host disease-like syndrome. J Exp Med. 1985 Jul 1;162(1):1–18. doi: 10.1084/jem.162.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Watanabe-Fukunaga R., Brannan C. I., Copeland N. G., Jenkins N. A., Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992 Mar 26;356(6367):314–317. doi: 10.1038/356314a0. [DOI] [PubMed] [Google Scholar]

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