The expression of early resistance to an infection with Mycobacterium tuberculosis by old mice is dependent on IFN type II (IFN-gamma) but not IFN type I

Mech Ageing Dev. 2004 Jan;125(1):1-9. doi: 10.1016/j.mad.2003.09.002.

Abstract

Old mice can express a transient early resistance to infection with M. tuberculosis that requires the presence of CD8 T cells within the lungs. Further characterization of those CD8 T cells within the aged lung established that the majority of CD8 T cells from old mice expressed the IL-15 receptor (CD122) in combination with bright expression of CD44 (CD44(hi)), and were capable of producing IFN-gamma after T cell receptor cross-linking. It has been previously described that CD8 CD44(hi) T cells proliferate in response to IFN-I, acting via IL-15, and therefore we determined whether IFN-I signaling could be a participant in the response of CD8 T cells within the lungs of old mice infected with M. tuberculosis. We demonstrate here that IFN-I signaling was required for the expansion of CD8 T cells within the aging lung in response to infection with M. tuberculosis, but that IFN-I signaling had no influence on the capacity of old mice to express early resistance to an infection with M. tuberculosis. Resident CD8 T cells were still however capable of producing IFN-gamma, which we demonstrate here to be critical in the expression of early resistance, suggesting that the expression of early resistance requires the participation, but not expansion, of the CD8 T cell pool within the aging lung.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging*
  • Animals
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Membrane / metabolism
  • Disease Susceptibility
  • Interferon Type I / metabolism*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / deficiency
  • Interferon-gamma / metabolism*
  • Lung / pathology
  • Membrane Proteins
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mycobacterium tuberculosis*
  • Receptor, Interferon alpha-beta
  • Receptors, Interferon / deficiency
  • Receptors, Interleukin-2 / metabolism
  • Tuberculosis / etiology*
  • Tuberculosis / metabolism*
  • Tuberculosis / pathology

Substances

  • Interferon Type I
  • Membrane Proteins
  • Receptors, Interferon
  • Receptors, Interleukin-2
  • Receptor, Interferon alpha-beta
  • Interferon-gamma