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. 1982 Sep 1;156(3):844–859. doi: 10.1084/jem.156.3.844

Generation of cytolytic T lymphocytes in thymectomized, irradiated, and bone marrow-reconstituted mice

PMCID: PMC2186799  PMID: 6125557

Abstract

A model system has been developed to study extrathymic T cell differentiation. Mice have been thymectomized, lethally irradiated, and reconstituted with bone marrow cells depleted of Thy-1-positive cells. After 8 wk, the spleen cells of these 5athymic, bone marrow- reconstituted chimeras contain Thy-1-positive pre-cytolytic T lymphocytes (CTL) that are able to respond to antigen only when exogenous interleukin 2 is added to culture.. The phenotype of these pre-CTL is similar to that of thymocytes, suggesting that they may be an immature T cell. Initial evaluation of the CTL repertoire of these athymic mice demonstrates that the CTL generated to trinitrophenyl- modified syngeneic cells are H-2 restricted and that the CTL generated to alloantigens have many of the cross-reactivities observed in normal but not in nude mice. The discrepancies observed in the CTL repertoire between these thymectomized chimeras and nude mice are discussed.

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Selected References

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  1. Abehsira O., Edwards A., Simpson E. Functional and binding activity of monoclonal anti-Thy-1 antibodies: evidence for different expression of the two alleles. Eur J Immunol. 1981 Apr;11(4):275–281. doi: 10.1002/eji.1830110402. [DOI] [PubMed] [Google Scholar]
  2. Ando I. Self-MHC-restricted cytotoxic T-cell response without thymic influence. Nature. 1981 Feb 5;289(5797):494–495. doi: 10.1038/289494a0. [DOI] [PubMed] [Google Scholar]
  3. Bevan M. J. In a radiation chimaera, host H-2 antigens determine immune responsiveness of donor cytotoxic cells. Nature. 1977 Sep 29;269(5627):417–418. doi: 10.1038/269417a0. [DOI] [PubMed] [Google Scholar]
  4. Burakoff S. J., Finberg R., Glimcher L., Lemonnier F., Benacerraf B., Cantor H. The biologic significance of alloreactivity. The ontogeny of T-cell sets specific for alloantigens or modified self antigens. J Exp Med. 1978 Nov 1;148(5):1414–1422. doi: 10.1084/jem.148.5.1414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burakoff S. J., Germain R. N., Benacerraf B. Cross-reactive lysis of trinitrophenyl (TNP)-derivatized H-2 incompatible target cells by cytolytic T lymphocytes generated against syngeneic TNP spleen cells. J Exp Med. 1976 Dec 1;144(6):1609–1620. doi: 10.1084/jem.144.6.1609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burakoff S. J., Germain R. N., Dorf M. E., Benacerrah B. Inhibition of cell-mediated cytolysis of trinitrophenyl-derivatized target cells by alloantisera directed to the products of the K and D loci of the H-2 complex. Proc Natl Acad Sci U S A. 1976 Feb;73(2):625–629. doi: 10.1073/pnas.73.2.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cantor H., Boyse E. A. Regulation of cellular and humoral immune responses by T-cell subclasses. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):23–32. doi: 10.1101/sqb.1977.041.01.006. [DOI] [PubMed] [Google Scholar]
  8. Cytolytic thymus-derived lymphocytes specific for allogeneic stimulator cells crossreact with chemically modified syngeneic cells. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1229–1233. doi: 10.1073/pnas.74.3.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Doherty P. C., Blanden R. V., Zinkernagel R. M. Specificity of virus-immune effector T cells for H-2K or H-2D compatible interactions: implications for H-antigen diversity. Transplant Rev. 1976;29:89–124. doi: 10.1111/j.1600-065x.1976.tb00198.x. [DOI] [PubMed] [Google Scholar]
  10. Fathman C. G., Small M., Herzenberg L. A., Weissman I. L. Thymus cell maturation. II. Differentiation of three "mature" subclasses in vivo. Cell Immunol. 1975 Jan;15(1):109–128. doi: 10.1016/0008-8749(75)90169-0. [DOI] [PubMed] [Google Scholar]
  11. Fink P. J., Bevan M. J. H-2 antigens of the thymus determine lymphocyte specificity. J Exp Med. 1978 Sep 1;148(3):766–775. doi: 10.1084/jem.148.3.766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Galli P., Dröge W. Development of cytotoxic T lymphocyte precursors in the absence of the thymus. Eur J Immunol. 1980 Feb;10(2):87–92. doi: 10.1002/eji.1830100204. [DOI] [PubMed] [Google Scholar]
  13. Gillis S., Union N. A., Baker P. E., Smith K. A. The in vitro generation and sustained culture of nude mouse cytolytic T-lymphocytes. J Exp Med. 1979 Jun 1;149(6):1460–1476. doi: 10.1084/jem.149.6.1460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gillis S., Watson J. Interleukin-2 induction of hapten-specific cytolytic T cells in nude mice. J Immunol. 1981 Apr;126(4):1245–1248. [PubMed] [Google Scholar]
  15. Hünig T., Bevan M. J. Self H-2 antigens influence the specificity of alloreactive cells. J Exp Med. 1980 May 1;151(5):1288–1298. doi: 10.1084/jem.151.5.1288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hünig T., Bevan M. J. Specificity of cytotoxic T cells from athymic mice. J Exp Med. 1980 Sep 1;152(3):688–702. doi: 10.1084/jem.152.3.688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Irlé C., Piguet P. F., Vassalli P. In vitro maturation of immature thymocytes into immunocompetent T cells in the absence of direct thymic influence. J Exp Med. 1978 Jul 1;148(1):32–45. doi: 10.1084/jem.148.1.32. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jordan R. K., Owen J. J., Raff M. C. Organ culture studies of nude mouse thymus. Eur J Immunol. 1977 Oct;7(10):736–743. doi: 10.1002/eji.1830071017. [DOI] [PubMed] [Google Scholar]
  19. Kruisbeek A. M., Sharrow S. O., Mathieson B. J., Singer A. The H-2 phenotype of the thymus dictates the self-specificity expressed by thymic but not splenic cytotoxic T lymphocyte precursors in thymus-engrafted nude mice. J Immunol. 1981 Nov;127(5):2168–2176. [PubMed] [Google Scholar]
  20. Lake J. P., Andrew M. E., Pierce C. W., Braciale T. J. Sendai virus-specific, H-2-restricted cytotoxic T lymphocyte responses of nude mice grafted with allogeneic or semi-allogeneic thymus glands. J Exp Med. 1980 Dec 1;152(6):1805–1810. doi: 10.1084/jem.152.6.1805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ledbetter J. A., Rouse R. V., Micklem H. S., Herzenberg L. A. T cell subsets defined by expression of Lyt-1,2,3 and Thy-1 antigens. Two-parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views. J Exp Med. 1980 Aug 1;152(2):280–295. doi: 10.1084/jem.152.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mier J. W., Gallo R. C. Purification and some characteristics of human T-cell growth factor from phytohemagglutinin-stimulated lymphocyte-conditioned media. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6134–6138. doi: 10.1073/pnas.77.10.6134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shearer G. M., Rehn T. G., Schmitt-Verhulst A. M. Role of the murine major histocompatibility complex in the specificity of in vitro T-cell-mediated lympholysis against chemically-modified autologous lymphocytes. Transplant Rev. 1976;29:222–246. doi: 10.1111/j.1600-065x.1976.tb00203.x. [DOI] [PubMed] [Google Scholar]
  24. Shortman K., Von Boehmer H., Lipp J., Hopper K. Subpopulations of T-lymphocytes. Physical separation, functional specialisation and differentiation pathways of sub-sets of thymocytes and thymus-dependent peripheral lymphocytes. Transplant Rev. 1975;25:163–210. [PubMed] [Google Scholar]
  25. Simpson E., Gordon R. D. Responsiveness to HY antigen Ir gene complementation and target cell specificity. Immunol Rev. 1977;35:59–75. doi: 10.1111/j.1600-065x.1977.tb00235.x. [DOI] [PubMed] [Google Scholar]
  26. Stutman O. Intrathymic and extrathymic T cell maturation. Immunol Rev. 1978;42:138–184. doi: 10.1111/j.1600-065x.1978.tb00261.x. [DOI] [PubMed] [Google Scholar]
  27. Wagner H., Hardt C., Bartlett R., Röllinghoff M., Pfizenmaier K. Intrathymic differentiation of cytotoxic T lymphocyte (CTL) precursors. I. The CTL immunocompetence of peanut agglutinin-positive (cortical) and negative (medullary) Lyt 123 thymocytes. J Immunol. 1980 Dec;125(6):2532–2538. [PubMed] [Google Scholar]
  28. Wagner H., Hardt C., Heeg K., Röllinghoff M., Pfizenmaier K. T-cell-derived helper factor allows in vivo induction of cytotoxic T cells in nu/nu mice. Nature. 1980 Mar 20;284(5753):278–278. doi: 10.1038/284278a0. [DOI] [PubMed] [Google Scholar]
  29. Zinkernagel R. M., Althage A., Waterfield E., Kindred B., Welsh R. M., Callahan G., Pincetl P. Restriction specificities, alloreactivity, and allotolerance expressed by T cells from nude mice reconstituted with H-2-compatible or -incompatible thymus grafts. J Exp Med. 1980 Feb 1;151(2):376–399. doi: 10.1084/jem.151.2.376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Klein P. A., Klein J. On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? J Exp Med. 1978 Mar 1;147(3):882–896. doi: 10.1084/jem.147.3.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Zinkernagel R. M., Callahan G. N., Klein J., Dennert G. Cytotoxic T cells learn specificity for self H-2 during differentiation in the thymus. Nature. 1978 Jan 19;271(5642):251–253. doi: 10.1038/271251a0. [DOI] [PubMed] [Google Scholar]

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