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. 1992 Nov 1;176(5):1291–1302. doi: 10.1084/jem.176.5.1291

Stimulation of mature unprimed CD8+ T cells by semiprofessional antigen- presenting cells in vivo

PMCID: PMC2119426  PMID: 1402675

Abstract

To test whether unprimed CD8+ cells can recognize class I alloantigens presented selectively on non-bone marrow (BM)-derived cells, unprimed parental strain CD8+ cells were transferred to long-term parent-->F1 BM chimeras prepared with supralethal irradiation. Host class I expression in the chimeras was undetectable on BM-derived cells and, in spleen, was limited to low-level staining of vascular endothelium and moderate staining of follicular dendritic cells (a population of nonhemopoietic cells in germinal centers). Despite this restricted expression of antigen, acute blood-to-lymph recirculation of parental strain T cells through the chimeras led to selective trapping of 95% of CD8+ cells reactive to normal F1 spleen antigen presenting cells (APC) in vitro. Subsequently, a small proportion of the trapped cells entered cell division and gave rise to effector cells expressing strong host- specific CTL activity. The activation of host-specific CD8+ cells was also prominent in double-irradiated chimeras, and cell separation studies showed that the effector cells were generated from resting precursor cells rather than from memory-phenotype cells. It is suggested that the non-BM-derived cells in the chimeras acted as semiprofessional APC. These cells were nonimmunogenic for most host- reactive CD8+ cells but were capable of stimulating a small subset of high-affinity T cells. The possible relevance of the data to the prolonged immunogenicity of vascularized allografts in humans is discussed.

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Selected References

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  1. Austyn J. M., Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol. 1981 Oct;11(10):805–815. doi: 10.1002/eji.1830111013. [DOI] [PubMed] [Google Scholar]
  2. Brodsky F. M., Guagliardi L. E. The cell biology of antigen processing and presentation. Annu Rev Immunol. 1991;9:707–744. doi: 10.1146/annurev.iy.09.040191.003423. [DOI] [PubMed] [Google Scholar]
  3. Bruce J., Symington F. W., McKearn T. J., Sprent J. A monoclonal antibody discriminating between subsets of T and B cells. J Immunol. 1981 Dec;127(6):2496–2501. [PubMed] [Google Scholar]
  4. Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
  5. Fabre J. W. Rat kidney allograft model: was it all too good to be true? Transplantation. 1982 Oct;34(4):223–225. [PubMed] [Google Scholar]
  6. Faustman D. L., Steinman R. M., Gebel H. M., Hauptfeld V., Davie J. M., Lacy P. E. Prevention of rejection of murine islet allografts by pretreatment with anti-dendritic cell antibody. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3864–3868. doi: 10.1073/pnas.81.12.3864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fink P. J., Bevan M. J., Weissman I. L. Thymic cytotoxic T lymphocytes are primed in vivo to minor histocompatibility antigens. J Exp Med. 1984 Feb 1;159(2):436–451. doi: 10.1084/jem.159.2.436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ford W. L., Simmonds S. J., Atkins R. C. Early cellular events in a systemic graft-vs.-host reaction. II. Autoradiographic estimates of the frequency of donor lymphocytes which respond to each Ag-B-determined antigenic complex. J Exp Med. 1975 Mar 1;141(3):681–696. doi: 10.1084/jem.141.3.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gao E. K., Kanagawa O., Sprent J. Capacity of unprimed CD4+ and CD8+ T cells expressing V beta 11 receptors to respond to I-E alloantigens in vivo. J Exp Med. 1989 Dec 1;170(6):1947–1957. doi: 10.1084/jem.170.6.1947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gao E. K., Kosaka H., Surh C. D., Sprent J. T cell contact with Ia antigens on nonhemopoietic cells in vivo can lead to immunity rather than tolerance. J Exp Med. 1991 Aug 1;174(2):435–446. doi: 10.1084/jem.174.2.435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gao E. K., Lo D., Sprent J. Strong T cell tolerance in parent----F1 bone marrow chimeras prepared with supralethal irradiation. Evidence for clonal deletion and anergy. J Exp Med. 1990 Apr 1;171(4):1101–1121. doi: 10.1084/jem.171.4.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Guttmann R. D., Beaudoin J. G., Morehouse D. D. Reduction of immunogenicity of human cadaver renal allografts by donor pretreatment. Transplant Proc. 1973 Mar;5(1):663–665. [PubMed] [Google Scholar]
  13. Hart D. N., Fabre J. W. Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain. J Exp Med. 1981 Aug 1;154(2):347–361. doi: 10.1084/jem.154.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Heath W. R., Hurd M. E., Carbone F. R., Sherman L. A. Peptide-dependent recognition of H-2Kb by alloreactive cytotoxic T lymphocytes. Nature. 1989 Oct 26;341(6244):749–752. doi: 10.1038/341749a0. [DOI] [PubMed] [Google Scholar]
  15. Jenkins M. K., Schwartz R. H. Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med. 1987 Feb 1;165(2):302–319. doi: 10.1084/jem.165.2.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lafferty K. J., Prowse S. J., Simeonovic C. J., Warren H. S. Immunobiology of tissue transplantation: a return to the passenger leukocyte concept. Annu Rev Immunol. 1983;1:143–173. doi: 10.1146/annurev.iy.01.040183.001043. [DOI] [PubMed] [Google Scholar]
  17. Larsen C. P., Morris P. J., Austyn J. M. Migration of dendritic leukocytes from cardiac allografts into host spleens. A novel pathway for initiation of rejection. J Exp Med. 1990 Jan 1;171(1):307–314. doi: 10.1084/jem.171.1.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lechler R. I., Batchelor J. R. Restoration of immunogenicity to passenger cell-depleted kidney allografts by the addition of donor strain dendritic cells. J Exp Med. 1982 Jan 1;155(1):31–41. doi: 10.1084/jem.155.1.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Malek T. R., Robb R. J., Shevach E. M. Identification and initial characterization of a rat monoclonal antibody reactive with the murine interleukin 2 receptor-ligand complex. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5694–5698. doi: 10.1073/pnas.80.18.5694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miyake K., Medina K. L., Hayashi S., Ono S., Hamaoka T., Kincade P. W. Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures. J Exp Med. 1990 Feb 1;171(2):477–488. doi: 10.1084/jem.171.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
  22. Ozato K., Mayer N., Sachs D. H. Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. J Immunol. 1980 Feb;124(2):533–540. [PubMed] [Google Scholar]
  23. Ozato K., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression. J Immunol. 1981 Jan;126(1):317–321. [PubMed] [Google Scholar]
  24. Sarmiento M., Glasebrook A. L., Fitch F. W. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol. 1980 Dec;125(6):2665–2672. [PubMed] [Google Scholar]
  25. Spiegel H., Herbst H., Niedobitek G., Foss H. D., Stein H. Follicular dendritic cells are a major reservoir for human immunodeficiency virus type 1 in lymphoid tissues facilitating infection of CD4+ T-helper cells. Am J Pathol. 1992 Jan;140(1):15–22. [PMC free article] [PubMed] [Google Scholar]
  26. Sprent J., Miller J. F. Activation of thymus cells by histocompatibility antigens. Nat New Biol. 1971 Sep 15;234(50):195–198. doi: 10.1038/newbio234195a0. [DOI] [PubMed] [Google Scholar]
  27. Sprent J., Schaefer M. Properties of purified T cell subsets. I. In vitro responses to class I vs. class II H-2 alloantigens. J Exp Med. 1985 Dec 1;162(6):2068–2088. doi: 10.1084/jem.162.6.2068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Steinman R. M. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–296. doi: 10.1146/annurev.iy.09.040191.001415. [DOI] [PubMed] [Google Scholar]
  29. Surh C. D., Gao E. K., Kosaka H., Lo D., Ahn C., Murphy D. B., Karlsson L., Peterson P., Sprent J. Two subsets of epithelial cells in the thymic medulla. J Exp Med. 1992 Aug 1;176(2):495–505. doi: 10.1084/jem.176.2.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Webb S. R., Li J. H., Wilson D. B., Sprent J. Capacity of small B cell-enriched populations to stimulate mixed lymphocyte reactions: marked differences between irradiated vs. mitomycin C-treated stimulators. Eur J Immunol. 1985 Jan;15(1):92–96. doi: 10.1002/eji.1830150118. [DOI] [PubMed] [Google Scholar]

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