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. 1984 Feb 1;159(2):436–451. doi: 10.1084/jem.159.2.436

Thymic cytotoxic T lymphocytes are primed in vivo to minor histocompatibility antigens

PMCID: PMC2187221  PMID: 6607314

Abstract

Potent cytotoxic T lymphocyte (CTL) activity can be derived from cultures of thymocyte responders and minor H different spleen cell stimulators. As is the case of the spleen cell response previously reported, this cytotoxic activity requires in vivo priming. We performed several experiments designed to determine whether the in vivo priming effect is due to the in situ priming of the thymocyte CTL precursors, to contamination of thymus cell preparations with cells of neighboring lymph nodes, or to the appearance in the thymus of antigen- reactive peripheral T cells. We show by depletion of peripheral cells with antilymphocyte serum and part body irradiation that recent thymic immigrants derived from the bone marrow contribute to the primed thymic response. Thymic CTL were primed in animals in which peripheral T cell responses were completely eliminated by repeated treatment in vivo with monoclonal anti-Thy-1 reagents. Primed, antigen-activated lymph node cells were also demonstrated to contribute to the thymus-derived CTL response. Thus, the minor H-specific thymic CTL response is due both to in situ priming and the immigration of activated peripheral T cells. We discuss the possible significance for models of T cell differentiation of the presence within the thymus of antigen and antigen-reactive mature T cells.

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Selected References

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  1. BURNET M. Role of the thymus and related organs in immunity. Br Med J. 1962 Sep 29;2(5308):807–811. doi: 10.1136/bmj.2.5308.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barclay A. N., Mayrhofer G. Bone marrow origin of Ia-positive cells in the medulla rat thymus. J Exp Med. 1981 Jun 1;153(6):1666–1671. doi: 10.1084/jem.153.6.1666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Besedovsky H. O., del Rey A., Sorkin E. Role of prethymic cells in acquisition of self-tolerance. J Exp Med. 1979 Dec 1;150(6):1351–1358. doi: 10.1084/jem.150.6.1351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bevan M. J., Fink P. J. The influence of thymus H-2 antigens on the specificity of maturing killer and helper cells. Immunol Rev. 1978;42:3–19. doi: 10.1111/j.1600-065x.1978.tb00256.x. [DOI] [PubMed] [Google Scholar]
  5. Bevan M. J., Langman R. E., Cohn M. H-2 antigen-specific cytotoxic T cells induced by concanavalin A: estimation of their relative frequency. Eur J Immunol. 1976 Mar;6(3):150–156. doi: 10.1002/eji.1830060303. [DOI] [PubMed] [Google Scholar]
  6. Bevan M. J. Minor H antigens introduced on H-2 different stimulating cells cross-react at the cytotoxic T cell level during in vivo priming. J Immunol. 1976 Dec;117(6):2233–2238. [PubMed] [Google Scholar]
  7. Bevan M. J. Priming for a cytotoxic response to minor histocompatibility antigens: antigen specificity and failure to demonstrate a carrier effect. J Immunol. 1977 Apr;118(4):1370–1374. [PubMed] [Google Scholar]
  8. Bevan M. J. The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens. J Exp Med. 1975 Dec 1;142(6):1349–1364. doi: 10.1084/jem.142.6.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bradley S. M., Morrissey P. J., Sharrow S. O., Singer A. Tolerance of thymocytes to allogeneic I region determinants encountered prethymically. Evidence for expression of anti-Ia receptors by T cell precursors before their entry into the thymus. J Exp Med. 1982 Jun 1;155(6):1638–1652. doi: 10.1084/jem.155.6.1638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cantor H., Weissman I. Development and function of subpopulations of thymocytes and T lymphocytes. Prog Allergy. 1976;20:1–64. [PubMed] [Google Scholar]
  11. Ceredig R., Glasebrook A. L., MacDonald H. R. Phenotypic and functional properties of murine thymocytes. I. Precursors of cytolytic T lymphocytes and interleukin 2-producing cells are all contained within a subpopulation of "mature" thymocytes as analyzed by monoclonal antibodies and flow microfluorometry. J Exp Med. 1982 Feb 1;155(2):358–379. doi: 10.1084/jem.155.2.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dennert G., Hyman R., Lesley J., Trowbridge I. S. Effects of cytotoxic monoclonal antibody specific for T200 glycoprotein on functional lymphoid cell populations. Cell Immunol. 1980 Aug 1;53(2):350–364. doi: 10.1016/0008-8749(80)90335-4. [DOI] [PubMed] [Google Scholar]
  13. Elliott E. V. A persistent lymphoid cell population in the thymus. Nat New Biol. 1973 Apr 4;242(118):150–152. doi: 10.1038/newbio242150a0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Fink P. J., Weissman I. L., Bevan M. J. Haplotype-specific suppression of cytotoxic T cell induction by antigen inappropriately presented on T cells. J Exp Med. 1983 Jan 1;157(1):141–154. doi: 10.1084/jem.157.1.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. GOWANS J. L., KNIGHT E. J. THE ROUTE OF RE-CIRCULATION OF LYMPHOCYTES IN THE RAT. Proc R Soc Lond B Biol Sci. 1964 Jan 14;159:257–282. doi: 10.1098/rspb.1964.0001. [DOI] [PubMed] [Google Scholar]
  17. Good M. F., Pyke K. W., Nossal G. J. Functional clonal deletion of cytotoxic T-lymphocyte precursors in chimeric thymus produced in vitro from embryonic Anlagen. Proc Natl Acad Sci U S A. 1983 May;80(10):3045–3049. doi: 10.1073/pnas.80.10.3045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gordon R. D., Simpson E., Samelson L. E. In vitro cell-mediated immune responses to the male specific(H-Y) antigen in mice. J Exp Med. 1975 Nov 1;142(5):1108–1120. doi: 10.1084/jem.142.5.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kyewski B. A., Rouse R. V., Kaplan H. S. Thymocyte rosettes: multicellular complexes of lymphocytes and bone marrow-derived stromal cells in the mouse thymus. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5646–5650. doi: 10.1073/pnas.79.18.5646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  21. Lepault F., Weissman I. L. An in vivo assay for thymus-homing bone marrow cells. Nature. 1981 Sep 10;293(5828):151–154. doi: 10.1038/293151a0. [DOI] [PubMed] [Google Scholar]
  22. Macphail S., Stutman O. Suppressor T cells activated in a primary in vitro response to non-major histocompatibility alloantigens. J Exp Med. 1982 Nov 1;156(5):1398–1414. doi: 10.1084/jem.156.5.1398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Marshak-Rothstein A., Fink P., Gridley T., Raulet D. H., Bevan M. J., Gefter M. L. Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus. J Immunol. 1979 Jun;122(6):2491–2497. [PubMed] [Google Scholar]
  24. Micklem H. S., Ford C. E., Evans E. P., Ogden D. A. Compartments and cell flows within the mouse haemopoietic system. I. Restricted interchange between haemopoietic sites. Cell Tissue Kinet. 1975 May;8(3):219–232. doi: 10.1111/j.1365-2184.1975.tb01221.x. [DOI] [PubMed] [Google Scholar]
  25. Miller J. F. Experimental thymology has come of age. Thymus. 1979 Sep;1(1-2):3–25. [PubMed] [Google Scholar]
  26. Miller R. G., Teh H. S., Harley E., Phillips R. A. Quantitative studies of the activation of cytotoxic lymphocyte precursor cells. Immunol Rev. 1977;35:38–58. doi: 10.1111/j.1600-065x.1977.tb00234.x. [DOI] [PubMed] [Google Scholar]
  27. Naparstek Y., Ben-Nun A., Holoshitz J., Reshef T., Frenkel A., Rosenberg M., Cohen I. R. T lymphocyte lines producing or vaccinating against autoimmune encephalomyelitis (EAE). Functional activation induces peanut agglutinin receptors and accumulation in the brain and thymus of line cells. Eur J Immunol. 1983 May;13(5):418–423. doi: 10.1002/eji.1830130513. [DOI] [PubMed] [Google Scholar]
  28. Naparstek Y., Holoshitz J., Eisenstein S., Reshef T., Rappaport S., Chemke J., Ben-Nun A., Cohen I. R. Effector T lymphocyte line cells migrate to the thymus and persist there. Nature. 1982 Nov 18;300(5889):262–264. doi: 10.1038/300262a0. [DOI] [PubMed] [Google Scholar]
  29. Opitz H. G., Opitz U., Hewlett G., Schlumberger H. D. A new model for investigations of T-cell functions in mice: differential immunosuppressive effects of two monoclonal anti-Thy-1.2 antibodies. Immunobiology. 1982 Feb;160(5):438–453. doi: 10.1016/S0171-2985(82)80007-7. [DOI] [PubMed] [Google Scholar]
  30. Raviola E., Karnovsky M. J. Evidence for a blood-thymus barrier using electron-opaque tracers. J Exp Med. 1972 Sep 1;136(3):466–498. doi: 10.1084/jem.136.3.466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Weissman I. L., Baird S., Gardner R. L., Papaioannou V. E., Raschke W. Normal and neoplastic maturation of T-lineage lymphocytes. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):9–21. doi: 10.1101/sqb.1977.041.01.005. [DOI] [PubMed] [Google Scholar]
  32. Weissman I. L. Thymus cell maturation. Studies on the origin of cortisone-resistant thymic lymphocytes. J Exp Med. 1973 Feb 1;137(2):504–510. doi: 10.1084/jem.137.2.504. [DOI] [PMC free article] [PubMed] [Google Scholar]

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