1887

Abstract

Following acute infection, murine cytomegalovirus (MCMV) replicates persistently in the salivary glands, despite the vigorous response of activated CD8 T cells that infiltrate this gland. Virus-specific CD8 T lymphocytes isolated from this organ were found to express the inhibitory CD94/NKG2A receptor that, in some virus models, confers an inhibitory response to cytotoxic T lymphocytes (CTLs). In response to MCMV infection, expression of the CD94/NKG2A ligand, Qa-1, increased dramatically in the submandibular gland (SMG) prior to upregulation of H-2D. However, there was no net negative impact on virus-specific T-cell function, as virus titres were similar in CD94 and CD94 mice. CD94/NKG2A expression, also known to inhibit apoptosis, did not influence the numbers of accumulated T, NK and NK T cells. These data indicate that expression of inhibitory CD94/NKG2A receptors does not account for the failure of MCMV-specific CTLs to clear the SMG of infection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82444-0
2007-05-01
2019-11-12
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/5/1440.html?itemId=/content/journal/jgv/10.1099/vir.0.82444-0&mimeType=html&fmt=ahah

References

  1. Arlettaz, L., Villard, J., de Rham, C., Degermann, S., Chapuis, B., Huard, B. & Roosnek, E. ( 2004; ). Activating CD94 : NKG2C and inhibitory CD94 : NKG2A receptors are expressed by distinct subsets of committed CD8+ TCR αβ lymphocytes. Eur J Immunol 34, 3456–3464.[CrossRef]
    [Google Scholar]
  2. Cavanaugh, V. J., Deng, Y., Birkenbach, M. P., Slater, J. S. & Campbell, A. E. ( 2003; ). Vigorous innate and virus-specific cytotoxic T-lymphocyte responses to murine cytomegalovirus in the submaxillary salivary gland. J Virol 77, 1703–1717.[CrossRef]
    [Google Scholar]
  3. Gold, M. C., Munks, M. W., Wagner, M., McMahon, C. W., Kelly, A., Kavanagh, D. G., Slifka, M. K., Koszinowski, U. H., Raulet, D. H. & Hill, A. B. ( 2004; ). Murine cytomegalovirus interference with antigen presentation has little effect on the size or the effector memory phenotype of the CD8 T cell response. J Immunol 172, 6944–6953.[CrossRef]
    [Google Scholar]
  4. Gunturi, A., Berg, R. E. & Forman, J. ( 2003; ). Preferential survival of CD8 T and NK cells expressing high levels of CD94. J Immunol 170, 1737–1745.[CrossRef]
    [Google Scholar]
  5. Gunturi, A., Berg, R. E. & Forman, J. ( 2004; ). The role of CD94/NKG2 in innate and adaptive immunity. Immunol Res 30, 29–34.[CrossRef]
    [Google Scholar]
  6. Jabri, B., Selby, J. M., Negulescu, H., Lee, L., Roberts, A. I., Beavis, A., Lopez-Botet, M., Ebert, E. C. & Winchester, R. J. ( 2002; ). TCR specificity dictates CD94/NKG2A expression by human CTL. Immunity 17, 487–499.[CrossRef]
    [Google Scholar]
  7. Jia, S. H., Kurepa, Z., Bai, A. & Forman, J. ( 2000; ). Comparative ability of Qdm/Qa-1b, Kb, and Db to protect class Ilow cells from NK-mediated lysis in vivo. J Immunol 165, 6142–6147.[CrossRef]
    [Google Scholar]
  8. Jonjic, S., Mutter, W., Weiland, F., Reddehase, M. J. & Koszinowski, U. H. ( 1989; ). Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes. J Exp Med 169, 1199–1212.[CrossRef]
    [Google Scholar]
  9. Karabekian, Z., Hanson, L. K., Slater, J. S., Krishna, N. K., Bolin, L. L., Kerry, J. A. & Campbell, A. E. ( 2005; ). Complex formation among murine cytomegalovirus US22 proteins encoded by genes M139, M140, and M141. J Virol 79, 3525–3535.[CrossRef]
    [Google Scholar]
  10. Lu, X., Pinto, A. K., Kelly, A. M., Cho, K. S. & Hill, A. B. ( 2006; ). Murine cytomegalovirus interference with antigen presentation contributes to the inability of CD8 T cells to control virus in the salivary gland. J Virol 80, 4200–4202.[CrossRef]
    [Google Scholar]
  11. McMahon, C. W., Zajac, A. J., Jamieson, A. M., Corral, L., Hammer, G. E., Ahmed, R. & Raulet, D. H. ( 2002; ). Viral and bacterial infections induce expression of multiple NK cell receptors in responding CD8+ T cells. J Immunol 169, 1444–1452.[CrossRef]
    [Google Scholar]
  12. Miller, J. D., Peters, M., Oran, A. E., Beresford, G. W., Harrington, L., Boss, J. M. & Altman, J. D. ( 2002; ). CD94/NKG2 expression does not inhibit cytotoxic function of lymphocytic choriomeningitis virus-specific CD8+ T cells. J Immunol 169, 693–701.[CrossRef]
    [Google Scholar]
  13. Moser, J. M., Gibbs, J., Jensen, P. E. & Lukacher, A. E. ( 2002; ). CD94-NKG2A receptors regulate antiviral CD8+ T cell responses. Nat Immunol 3, 189–195.[CrossRef]
    [Google Scholar]
  14. Pavic, I., Polic, B., Crnkovic, I., Lucin, P., Jonjic, S. & Koszinowski, U. H. ( 1993; ). Participation of endogenous tumour necrosis factor alpha in host resistance to cytomegalovirus infection. J Gen Virol 74, 2215–2223.[CrossRef]
    [Google Scholar]
  15. Suvas, S., Azkur, A. K. & Rouse, B. T. ( 2006; ). Qa-1b and CD94-NKG2a interaction regulate cytolytic activity of herpes simplex virus-specific memory CD8+ T cells in the latently infected trigeminal ganglia. J Immunol 176, 1703–1711.[CrossRef]
    [Google Scholar]
  16. Vance, R. E., Jamieson, A. M. & Raulet, D. H. ( 1999; ). Recognition of the class Ib molecule Qa-1b by putative activating receptors CD94/NKG2C and CD94/NKG2E on mouse natural killer cells. J Exp Med 190, 1801–1812.[CrossRef]
    [Google Scholar]
  17. Vance, R. E., Jamieson, A. M., Cado, D. & Raulet, D. H. ( 2002; ). Implications of CD94 deficiency and monoallelic NKG2A expression for natural killer cell development and repertoire formation. Proc Natl Acad Sci U S A 99, 868–873.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.82444-0
Loading
/content/journal/jgv/10.1099/vir.0.82444-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error