Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1981 Jan 1;153(1):13–29. doi: 10.1084/jem.153.1.13

Cytotoxic T lymphocyte responses by chimeric thymocytes. Self- recognition is determined early in T cell development

PMCID: PMC2186059  PMID: 6969780

Abstract

In this study the cytotoxic T lymphocyte (CTL) recognition pattern of thymocytes from recently reconstituted parent leads to F1 and F1 leads to parent radiation bone marrow chimeras was investigated. Chimeric thymocytes were entirely of donor origin approximately 4 wk after irradiation and reconstitution but were not capable of autonomously generating either alloreactive or trinitrophenyl (TNP)-modified-self- reactive CTL responses. However, in the presence of interleukin-2 (I1- 2), the the putative T helper cell product, CTL could be generated in vitro by thymocytes from recently reconstituted chimeras. Experiments with thymocytes from A leads to A X B and A X B leads to A chimeras revealed the following: (a) thymocytes from both types of chimeras were nonreactive to either A or B parental major-histocompatibility complex (MHC) determinants even though they were alloreactive to third-party stimulator cells; and (b) thymocytes from these chimeras were restricted to the recognition of TNP in association with MHC determinants syngeneic to the chimeric host. Thus, these experiments demonstrate that even at the earliest time CTL effectors of donor origin from the thymuses of chimeras can be studied, their self- receptor repertoire has already been restricted to recognition of host MHC determinants. These results support the concept that the host environment influences the self-recognition capacity of T cells at the pre- or intrathymic stage of differentiation.

Full Text

The Full Text of this article is available as a PDF (999.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beller D. I., Unanue E. R. IA antigens and antigen-presenting function of thymic macrophages. J Immunol. 1980 Mar;124(3):1433–1440. [PubMed] [Google Scholar]
  2. 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]
  3. Billings P., Burakoff S. J., Dorf M. E., Benacerraf B. Genetic control of cytolytic T-lymphocyte responses. I. Ir gene control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells. J Exp Med. 1978 Aug 1;148(2):341–350. doi: 10.1084/jem.148.2.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Billings P., Burakoff S. J., Dorf M. E., Benacerraf B. Genetic control of cytolytic t-lymphocyte responses. II. The role of the host genotype in parental leads to F1 radiation chimeras in the control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells. J Exp Med. 1978 Aug 1;148(2):352–359. doi: 10.1084/jem.148.2.352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blanden R. V., Andrew M. E. Primary anti-viral cytotoxic T-cell responses in semiallogeneic chimeras are not absolutely restricted to host H-2 type. J Exp Med. 1979 Feb 1;149(2):535–538. doi: 10.1084/jem.149.2.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Doherty P. C., Bennink J. C. Vaccinia-specific cytotoxic T-cell responses in the context of H-2 antigens not encountered in thymus may reflect aberrant recognition of a virus-H-2 complex. J Exp Med. 1979 Jan 1;149(1):150–157. doi: 10.1084/jem.149.1.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Farrar J. J., Simon P. L., Koopman W. J., Fuller-Bonar J. Biochemical relationship of thymocyte mitogenic factor and factors enhancing humoral and cell-mediated immune responses. J Immunol. 1978 Oct;121(4):1353–1360. [PubMed] [Google Scholar]
  10. 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]
  11. Hodes R. J., Hathcock K. S., Singer A. Cellular and genetic control of antibody responses. VII. Absence of detectable suppression maintaining the H-2 restricted recognition of F1 leads to parent helper T cells. J Immunol. 1980 Jan;124(1):134–139. [PubMed] [Google Scholar]
  12. Hodes R. J., Singer A. Cellular and genetic control of antibody responses in vitro. I. Cellular requirements for the generation of genetically controlled primary IgM responses to soluble antigens. Eur J Immunol. 1977 Dec;7(12):892–897. doi: 10.1002/eji.1830071214. [DOI] [PubMed] [Google Scholar]
  13. Kadish J. L., Basch R. S. Thymic regeneration after lethal irradiation evidence for an intra-thymic radioresistant T cell precursor. J Immunol. 1975 Jan;114(1 Pt 2):452–458. [PubMed] [Google Scholar]
  14. Kappler J. W., Marrack P. The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression. J Exp Med. 1978 Dec 1;148(6):1510–1522. doi: 10.1084/jem.148.6.1510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kruisbeek A. M., Zijlstra J. J., Kröse T. J. Distinct effects of T cell growth factors and thymic epithelial factors on the generation of cytotoxic T lymphocytes by thymocyte subpopulations. J Immunol. 1980 Sep;125(3):995–1002. [PubMed] [Google Scholar]
  16. Okada M., Klimpel G. R., Kuppers R. C., Henney C. S. The differentiation of cytotoxic T cells in vitro. I. Amplifying factor(s) in the primary response is Lyt 1 + cell dependent. J Immunol. 1979 Jun;122(6):2527–2533. [PubMed] [Google Scholar]
  17. Pfizenmaier K., Strazinski-Powitz A., Rodt H., Röllinghoff M., Wagner H. Virus and trinitrophenol hapten-specific T-cell-mediated cytotoxicity against H-2 incompatible target cells. J Exp Med. 1976 Apr 1;143(4):999–1004. doi: 10.1084/jem.143.4.999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rouse R. V., van Ewijk W., Jones P. P., Weissman I. L. Expression of MHC antigens by mouse thymic dendritic cells. J Immunol. 1979 Jun;122(6):2508–2515. [PubMed] [Google Scholar]
  19. Shaw J., Monticone V., Mills G., Paetkau V. Effects of costimulator on immune responses in vitro. J Immunol. 1978 Jun;120(6):1974–1980. [PubMed] [Google Scholar]
  20. Shearer G. M. Cell-mediated cytotoxicity to trinitrophenyl-modified syngeneic lymphocytes. Eur J Immunol. 1974 Aug;4(8):527–533. doi: 10.1002/eji.1830040802. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Shearer G. M., Schmitt-Verhulst A. M., Pettinelli C. B., Miller M. W., Gilheany P. E. H-2-linked genetic control of murine T-cell-mediated lympholysis to autologous cells modified with low concentrations of trinitrobenzene sulfonate. J Exp Med. 1979 Jun 1;149(6):1407–1423. doi: 10.1084/jem.149.6.1407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Singer A., Hathcock K. S., Hodes R. J. Cellular and genetic control of antibody responses. V. Helper T-cell recognition of H-2 determinants on accessory cells but not B cells. J Exp Med. 1979 May 1;149(5):1208–1226. doi: 10.1084/jem.149.5.1208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wagner H., Räollinghoff M., Pfizenmaier K., Hardt C., Johnscher G. T-T cell interactions during in vitro cytotoxic T lymphocyte (CTL) responses. II. Helper factor from activated Lyt 1+ T cells is rate limiting i) in T cell responses to nonimmunogenic alloantigen, ii) in thymocyte responses to allogeneic stimulator cells, and III) recruits allo- or H-2-restricted CTL precursors from the Lyt 123+ T subset. J Immunol. 1980 Mar;124(3):1058–1067. [PubMed] [Google Scholar]
  25. Wagner H., Röllinghoff M. T-T-cell interactions during the vitro cytotoxic allograft responses. I. Soluble products from activated Lyl+ T cells trigger autonomously antigen-primed Ly23+ T cells to cell proliferation and cytolytic activity. J Exp Med. 1978 Dec 1;148(6):1523–1538. doi: 10.1084/jem.148.6.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wekerle H., Ketelsen U. P., Ernst M. Thymic nurse cells. Lymphoepithelial cell complexes in murine thymuses: morphological and serological characterization. J Exp Med. 1980 Apr 1;151(4):925–944. doi: 10.1084/jem.151.4.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wekerle H., Ketelsen U. P. Thymic nurse cells--Ia-bearing epithelium involved in T-lymphocyte differentiation? Nature. 1980 Jan 24;283(5745):402–404. doi: 10.1038/283402a0. [DOI] [PubMed] [Google Scholar]
  28. Wilson D. B., Lindahl K. F., Wilson D. H., Sprent J. The generation of killer cells to trinitrophenyl-modified allogeneic targets by lymphocyte populations negatively selected to strong alloantigens. J Exp Med. 1977 Aug 1;146(2):361–367. doi: 10.1084/jem.146.2.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zinkernagel R. M., Althage A. Search for suppression of T cells specific for the second nonhost H-2 haplotype in F1 leads to P irradiation bone marrow chimeras. J Immunol. 1979 May;122(5):1742–1749. [PubMed] [Google Scholar]
  30. 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]
  31. 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]
  32. 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]
  33. Zinkernagel R. M. H-2 restriction of virus-specific cytotoxicity across the H-2 barrier. Separate effector T-cell specificities are associated with self-H-2 and with the tolerated allogeneic H-2 in chimeras. J Exp Med. 1976 Oct 1;144(4):933–945. doi: 10.1084/jem.144.4.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zinkernagel R. M. Thymus and lymphohemopoietic cells: their role in T cell maturation in selection of T cells' H-2-restriction-specificity and in H-2 linked Ir gene control. Immunol Rev. 1978;42:224–270. doi: 10.1111/j.1600-065x.1978.tb00264.x. [DOI] [PubMed] [Google Scholar]
  35. von Boehmer H., Haas W., Pohlit H. Cytotoxic T cells recognize male antigen and H-2 as distinct entities. J Exp Med. 1978 Apr 1;147(4):1291–1295. doi: 10.1084/jem.147.4.1291. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES