Skip to main content
Immunology logoLink to Immunology
. 1997 Aug;91(4):511–519. doi: 10.1046/j.1365-2567.1997.00303.x

TCR alpha beta+ CD4- CD8- T cells differentiate extrathymically in an lck-independent manner and participate in early response against Listeria monocytogenes infection through interferon-gamma production.

T Kadena 1, G Matsuzaki 1, S Fujise 1, K Kishihara 1, H Takimoto 1, M Sasaki 1, M Beppu 1, S Nakamura 1, K Nomoto 1
PMCID: PMC1363869  PMID: 9378488

Abstract

T-cell receptor (TCR) alpha beta+ CD4- CD8- (double-negative; DN) T cells appear in the peritoneal cavity at an early stage of intraperitoneal (i.p.) infection with the intracellular pathogen Listeria monocytogenes. In the present report, we analysed the developmental pathway and functions of the TCR alpha beta+ DN T cells using the L. monocytogenes infection system. The TCR alpha beta+ DN T cells appeared in the peritoneal cavity after L. monocytogenes i.p. infection in adult-thymectomized lethally irradiated bone marrow chimeras and p56lck-deficient mice. The results demonstrated that the TCR alpha beta+ DN T cells can develop extrathymically in a p56lck-independent manner. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that the TCR alpha beta+ DN T cells expressed genes for interferon-gamma (IFN-gamma), the macrophage chemotactic factors MCP-1 and Eta-1, and granulocyte-macrophage colony-stimulating factor (GM-CSF) but lacked expression of genes for interleukin-2 (IL-2), IL-4 and IL-10. As expected from the RT-PCR analysis, the TCR alpha beta+ DN T cells produced IFN-gamma in response to anti-TCR beta monoclonal antibody (mAb), anti-CD3 mAb and L. monocytogenes-infected macrophages but IL-4 was undetectable after the stimulation. Furthermore, the intracellular cytokine staining analysis demonstrated that approximately half of the TCR alpha beta+ DN T cells detectable at the early stage of L. monocytogenes infection were IFN-gamma-producing cells. All of the results suggest that the TCR alpha beta+ DN T cells develop through a unique extrathymic p56lck-independent pathway and participate in early protection against bacterial infection through activation and accumulation of macrophages.

Full text

PDF
511

Images in this article

Selected References

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

  1. Anderson S. J., Abraham K. M., Nakayama T., Singer A., Perlmutter R. M. Inhibition of T-cell receptor beta-chain gene rearrangement by overexpression of the non-receptor protein tyrosine kinase p56lck. EMBO J. 1992 Dec;11(13):4877–4886. doi: 10.1002/j.1460-2075.1992.tb05594.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ballas Z. K., Rasmussen W. NK1.1+ thymocytes. Adult murine CD4-, CD8- thymocytes contain an NK1.1+, CD3+, CD5hi, CD44hi, TCR-V beta 8+ subset. J Immunol. 1990 Aug 15;145(4):1039–1045. [PubMed] [Google Scholar]
  3. Beckman E. M., Porcelli S. A., Morita C. T., Behar S. M., Furlong S. T., Brenner M. B. Recognition of a lipid antigen by CD1-restricted alpha beta+ T cells. Nature. 1994 Dec 15;372(6507):691–694. doi: 10.1038/372691a0. [DOI] [PubMed] [Google Scholar]
  4. Budd R. C., Miescher G. C., Howe R. C., Lees R. K., Bron C., MacDonald H. R. Developmentally regulated expression of T cell receptor beta chain variable domains in immature thymocytes. J Exp Med. 1987 Aug 1;166(2):577–582. doi: 10.1084/jem.166.2.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Crispe I. N. CD4/CD8-negative T cells with alpha beta antigen receptors. Curr Opin Immunol. 1994 Jun;6(3):438–441. doi: 10.1016/0952-7915(94)90124-4. [DOI] [PubMed] [Google Scholar]
  6. Dellabona P., Casorati G., Friedli B., Angman L., Sallusto F., Tunnacliffe A., Roosneek E., Lanzavecchia A. In vivo persistence of expanded clones specific for bacterial antigens within the human T cell receptor alpha/beta CD4-8- subset. J Exp Med. 1993 Jun 1;177(6):1763–1771. doi: 10.1084/jem.177.6.1763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ferrick D. A., Schrenzel M. D., Mulvania T., Hsieh B., Ferlin W. G., Lepper H. Differential production of interferon-gamma and interleukin-4 in response to Th1- and Th2-stimulating pathogens by gamma delta T cells in vivo. Nature. 1995 Jan 19;373(6511):255–257. doi: 10.1038/373255a0. [DOI] [PubMed] [Google Scholar]
  8. Fowlkes B. J., Kruisbeek A. M., Ton-That H., Weston M. A., Coligan J. E., Schwartz R. H., Pardoll D. M. A novel population of T-cell receptor alpha beta-bearing thymocytes which predominantly expresses a single V beta gene family. Nature. 1987 Sep 17;329(6136):251–254. doi: 10.1038/329251a0. [DOI] [PubMed] [Google Scholar]
  9. Glaichenhaus N., Shastri N., Littman D. R., Turner J. M. Requirement for association of p56lck with CD4 in antigen-specific signal transduction in T cells. Cell. 1991 Feb 8;64(3):511–520. doi: 10.1016/0092-8674(91)90235-q. [DOI] [PubMed] [Google Scholar]
  10. Gray M. L., Killinger A. H. Listeria monocytogenes and listeric infections. Bacteriol Rev. 1966 Jun;30(2):309–382. doi: 10.1128/br.30.2.309-382.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Guidos C. J., Weissman I. L., Adkins B. Developmental potential of CD4-8- thymocytes. Peripheral progeny include mature CD4-8- T cells bearing alpha beta T cell receptor. J Immunol. 1989 Jun 1;142(11):3773–3780. [PubMed] [Google Scholar]
  12. Hatakeyama M., Kono T., Kobayashi N., Kawahara A., Levin S. D., Perlmutter R. M., Taniguchi T. Interaction of the IL-2 receptor with the src-family kinase p56lck: identification of novel intermolecular association. Science. 1991 Jun 14;252(5012):1523–1528. doi: 10.1126/science.2047859. [DOI] [PubMed] [Google Scholar]
  13. Hiromatsu K., Yoshikai Y., Matsuzaki G., Ohga S., Muramori K., Matsumoto K., Bluestone J. A., Nomoto K. A protective role of gamma/delta T cells in primary infection with Listeria monocytogenes in mice. J Exp Med. 1992 Jan 1;175(1):49–56. doi: 10.1084/jem.175.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Iiai T., Watanabe H., Seki S., Sugiura K., Hirokawa K., Utsuyama M., Takahashi-Iwanaga H., Iwanaga T., Ohteki T., Abo T. Ontogeny and development of extrathymic T cells in mouse liver. Immunology. 1992 Dec;77(4):556–563. [PMC free article] [PubMed] [Google Scholar]
  15. Katsikis P. D., Cohen S. B., Murison J. G., Uren J., Hibbart L. M., Callard R. E., Di Padova F., Feldmann M., Londei M. Human alpha beta T-cell receptor CD4-CD8 T-cell clones are predominantly Th0-like. Immunology. 1995 Apr;84(4):501–504. [PMC free article] [PubMed] [Google Scholar]
  16. Kaufmann S. H., Simon M. M., Hahn H. Regulatory interactions between macrophages and T-cell subsets in Listeria monocytogenes-specific T-cell activation. Infect Immun. 1982 Dec;38(3):907–913. doi: 10.1128/iai.38.3.907-913.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kenai H., Matsuzaki G., Lin T., Yoshida H., Nomoto K. Precursor cells to CD3-intermediate (CD3int) liver mononuclear cells in the adult liver: further evidence for the extrathymic development of CD3int liver mononuclear cells. Eur J Immunol. 1995 Dec;25(12):3365–3369. doi: 10.1002/eji.1830251224. [DOI] [PubMed] [Google Scholar]
  18. Kenai H., Yoshikai Y., Matsuzaki G., Iwasaki A., Yuuki H., Nakamura T., Nomoto K. Appearance of extrathymic early differentiated CD4-CD8- T cells with T cell receptor gamma/delta or alpha/beta after thymus grafting to nude mice: influence of thymus on extrathymic T cell differentiation. Cell Immunol. 1994 Jan;153(1):79–93. doi: 10.1006/cimm.1994.1007. [DOI] [PubMed] [Google Scholar]
  19. Kikly K., Dennert G. Evidence for extrathymic development of TNK cells. NK1+ CD3+ cells responsible for acute marrow graft rejection are present in thymus-deficient mice. J Immunol. 1992 Jul 15;149(2):403–412. [PubMed] [Google Scholar]
  20. Koyasu S. CD3+CD16+NK1.1+B220+ large granular lymphocytes arise from both alpha-beta TCR+CD4-CD8- and gamma-delta TCR+CD4-CD8- cells. J Exp Med. 1994 Jun 1;179(6):1957–1972. doi: 10.1084/jem.179.6.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Leite-de-Moraes M. C., Herbelin A., Machavoine F., Vicari A., Gombert J. M., Papiernik M., Dy M. MHC class I-selected CD4-CD8-TCR-alpha beta+ T cells are a potential source of IL-4 during primary immune response. J Immunol. 1995 Nov 15;155(10):4544–4550. [PubMed] [Google Scholar]
  22. Levin S. D., Anderson S. J., Forbush K. A., Perlmutter R. M. A dominant-negative transgene defines a role for p56lck in thymopoiesis. EMBO J. 1993 Apr;12(4):1671–1680. doi: 10.1002/j.1460-2075.1993.tb05812.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Levitsky H. I., Golumbek P. T., Pardoll D. M. The fate of CD4-8- T cell receptor-alpha beta+ thymocytes. J Immunol. 1991 Feb 15;146(4):1113–1117. [PubMed] [Google Scholar]
  24. MACKANESS G. B. Cellular resistance to infection. J Exp Med. 1962 Sep 1;116:381–406. doi: 10.1084/jem.116.3.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Makino Y., Yamagata N., Sasho T., Adachi Y., Kanno R., Koseki H., Kanno M., Taniguchi M. Extrathymic development of V alpha 14-positive T cells. J Exp Med. 1993 May 1;177(5):1399–1408. doi: 10.1084/jem.177.5.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Matsuzaki G., Li X. Y., Kadena T., Song F., Hiromatsu K., Yoshida H., Nomoto K. Early appearance of T cell receptor alpha beta + CD4- CD8- T cells with a skewed variable region repertoire after infection with Listeria monocytogenes. Eur J Immunol. 1995 Jul;25(7):1985–1991. doi: 10.1002/eji.1830250728. [DOI] [PubMed] [Google Scholar]
  27. Mitsuyama M., Takeya K., Nomoto K., Shimotori S. Three phases of phagocyte contribution to resistance against Listeria monocytogenes. J Gen Microbiol. 1978 May;106(1):165–171. doi: 10.1099/00221287-106-1-165. [DOI] [PubMed] [Google Scholar]
  28. Miyata M., Mitsuyama M., Ogata N., Nomoto K. Protective mechanisms against infection by Listeria monocytogenes: accumulation and activation of macrophages. J Clin Lab Immunol. 1984 Mar;13(3):111–115. [PubMed] [Google Scholar]
  29. Molina T. J., Kishihara K., Siderovski D. P., van Ewijk W., Narendran A., Timms E., Wakeham A., Paige C. J., Hartmann K. U., Veillette A. Profound block in thymocyte development in mice lacking p56lck. Nature. 1992 May 14;357(6374):161–164. doi: 10.1038/357161a0. [DOI] [PubMed] [Google Scholar]
  30. Nomoto K., Taniguchi K., Kubo C., Takeya K. Relationships among differentiated T-cell subpopulations. III. Radioresistance of delayed hypersensitivity to heterologous erythrocytes. Immunology. 1978 Mar;34(3):517–521. [PMC free article] [PubMed] [Google Scholar]
  31. Ohga S., Yoshikai Y., Takeda Y., Hiromatsu K., Nomoto K. Sequential appearance of gamma/delta- and alpha/beta-bearing T cells in the peritoneal cavity during an i.p. infection with Listeria monocytogenes. Eur J Immunol. 1990 Mar;20(3):533–538. doi: 10.1002/eji.1830200311. [DOI] [PubMed] [Google Scholar]
  32. Reimann J. Double-negative (CD4-CD8-), TCR alpha beta-expressing, peripheral T cells. Scand J Immunol. 1991 Dec;34(6):679–688. doi: 10.1111/j.1365-3083.1991.tb01592.x. [DOI] [PubMed] [Google Scholar]
  33. Seki S., Abo T., Ohteki T., Sugiura K., Kumagai K. Unusual alpha beta-T cells expanded in autoimmune lpr mice are probably a counterpart of normal T cells in the liver. J Immunol. 1991 Aug 15;147(4):1214–1221. [PubMed] [Google Scholar]
  34. Shaw A. S., Amrein K. E., Hammond C., Stern D. F., Sefton B. M., Rose J. K. The lck tyrosine protein kinase interacts with the cytoplasmic tail of the CD4 glycoprotein through its unique amino-terminal domain. Cell. 1989 Nov 17;59(4):627–636. doi: 10.1016/0092-8674(89)90008-1. [DOI] [PubMed] [Google Scholar]
  35. Sieling P. A., Chatterjee D., Porcelli S. A., Prigozy T. I., Mazzaccaro R. J., Soriano T., Bloom B. R., Brenner M. B., Kronenberg M., Brennan P. J. CD1-restricted T cell recognition of microbial lipoglycan antigens. Science. 1995 Jul 14;269(5221):227–230. doi: 10.1126/science.7542404. [DOI] [PubMed] [Google Scholar]
  36. Song F., Matsuzaki G., Mitsuyama M., Nomoto K. Differential effects of viable and killed bacteria on IL-12 expression of macrophages. J Immunol. 1996 Apr 15;156(8):2979–2984. [PubMed] [Google Scholar]
  37. Sykes M. Unusual T cell populations in adult murine bone marrow. Prevalence of CD3+CD4-CD8- and alpha beta TCR+NK1.1+ cells. J Immunol. 1990 Nov 15;145(10):3209–3215. [PubMed] [Google Scholar]
  38. Takeuchi Y., Tanaka T., Hamamura K., Sugimoto T., Miyasaka M., Yagita H., Okumura K. Expression and role of interleukin-2 receptor beta chain on CD4-CD8- T cell receptor alpha beta+ cells [corrected]. Eur J Immunol. 1992 Nov;22(11):2929–2935. doi: 10.1002/eji.1830221126. [DOI] [PubMed] [Google Scholar]
  39. Veillette A., Bookman M. A., Horak E. M., Bolen J. B. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell. 1988 Oct 21;55(2):301–308. doi: 10.1016/0092-8674(88)90053-0. [DOI] [PubMed] [Google Scholar]
  40. Zlotnik A., Godfrey D. I., Fischer M., Suda T. Cytokine production by mature and immature CD4-CD8- T cells. Alpha beta-T cell receptor+ CD4-CD8- T cells produce IL-4. J Immunol. 1992 Aug 15;149(4):1211–1215. [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES