A Dichotomy Between the Cytolytic Activity and Antigen-Induced Proliferative Response of Human γδ T Cells

  • J. Holoshitz
  • N. K. Bayne
  • D. R. McKinley
  • Y. Jia
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 173)

Abstract

T cells bearing the γδ T cell receptor have been commonly found to display non-MHC-restricted, NK-like cytolytic activity (Moingeon 1987, Bosnes 1989, Fisch 1990). Other subsets of γδ T cells proliferate in response to mycobacterial antigens, in particular the 65 kd heat shock protein (HSP) of mycobacteria (Holoshitz 1989, Modlin 1989, Haregewoin 1989, O’Brien 1989, Janis 1989, Kabelitz 1990). We have previously reported four CD4-CD8- γδ T cell clones isolated from the synovial fluid of a patient with rheumatoid arthritis. These clones were selected by virtue of their proliferative response to mycobacteria and were found to recognize the mycobacterial HSP65. Their reactivity to mycobacteria was not restricted by MHC. In the present report we studied the cytolytic activity of these cells. We found that our γδ T cells display “promiscuous” non-MHC-restricted cytolytic activity against neoplastic cells. The cytolytic activity was not directed against exogenously added HSP65 or endogenous HSPs induced by heat. These results suggest that the cytolytic activity and recognition of soluble antigens are two distinct functional properties.

Keywords

Arthritis Acetone Lymphoma Leukemia Tuberculosis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bosnes V et al. (1989) Specificity of γδ receptor-bearing cytotoxic T lymphocytes isolated from human peripheral blood. Scand J Immunol 29:723–731.PubMedCrossRefGoogle Scholar
  2. De Bruyn J et al. (1987a) Purification, partial characterization, and identification of a skin-reactive protein antigen of Mycobacterium bovis BCG. Infect Immun 55:245–252.PubMedGoogle Scholar
  3. De Bruyn J et al. (1987) Purification, characterization and identification of a 32 kDa protein antigen of Mycobacterium bovis BCG. Microb Path 2:351–366.CrossRefGoogle Scholar
  4. Fisch P et al. (1990) γ/δ T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis. J Exp Med 171:1567–1579.PubMedCrossRefGoogle Scholar
  5. Grimm EA, Rosenberg SA (1984) The lymphokine activated killer phenomenon. In: Pick, E (ed) The Lymphokine, Vol 9. Academic Press, New York, p 279.Google Scholar
  6. Gromkowski SH, Hepler KM, Janeway CA (1988) Low doses of interleukin 2 induce bystander cell lysis by antigen-specific CD4+ inflammatory T cell clones in short-term assay. Eur J Immunol 18:1385–1389.PubMedCrossRefGoogle Scholar
  7. Haregewoin A et al. (1989) Human γδ+ T cells respond to mycobacterial heat-shock protein. Nature 340:309–312.PubMedCrossRefGoogle Scholar
  8. Holoshitz J et al. (1986) T lymphocytes of rheumatoid arthritis patients show augmented reactivity to a fraction of mycobacteria cross reactive with cartilage. Lancet II 305–309.CrossRefGoogle Scholar
  9. Holoshitz J et al. (1989) Isolation of CD4-CD8-mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Nature 339:226–229.PubMedCrossRefGoogle Scholar
  10. Janis EM et al. (1989) Activation of γδ T cells in the primary immune response to mycobacterium tuberculosis. Science 244:713–716.PubMedCrossRefGoogle Scholar
  11. Kabelitz D et al. (1990) A large fraction of human peripheral blood γδ+ T cells in activated by mycobacterium tuberculosis but not by its 65-kd heat shock protein. J Exp Med 171:667–679.PubMedCrossRefGoogle Scholar
  12. Modlin RL et al. (1989) Lymphocytes bearing antigen specific γδ T cell receptors accumulate in human infectious disease lesions. Nature 339:544–548.PubMedCrossRefGoogle Scholar
  13. Moingeon P et al. (1987) A γ-chain complex forms a functional receptor on cloned human lymphocytes with natural killer-like activity. Nature 325:723–726.PubMedCrossRefGoogle Scholar
  14. O’Brien RL et al. (1989) Stimulation of a major subset of lymphocytes expressing T cell receptor γδ by an antigen derived from Mycobacterium tuberculosis. Cell 57:667–674.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1991

Authors and Affiliations

  • J. Holoshitz
    • 1
  • N. K. Bayne
    • 1
  • D. R. McKinley
    • 1
  • Y. Jia
    • 1
  1. 1.Department of Internal MedicineUniversity of Michigan School of MedicineAnn ArborUSA

Personalised recommendations