Anergy, IFN-gamma production, and apoptosis in terminal infection of mice with Mycobacterium avium.

  • 15 August 1999
    • journal article
    • Vol. 163  (4) , 2073-80
Abstract
We have followed the course of experimental infection of mice with Mycobacterium avium over an extended period, assessing bacterial numbers and T cell responsiveness. When mice were infected intranasally, bacteria spread to the spleen and liver, but remained in highest numbers in the lungs. Both CD4+ and CD8+ T cells, assayed at any time from 6-28 wk after infection, produced IFN-gamma. After initial rapid growth, bacterial numbers slowly increased from approximately 107 at 6 wk to more than 5 x 108 at 28 wk, indicating that the resistance mechanisms so generated were not adequate to contain the infection. During infection, apoptosis of both CD4+ and CD8+ T cells, measured immediately ex vivo by staining with Annexin V, increased steadily. With some individual exceptions, there was a close correlation between apoptosis of CD4+ cells and level of IFN-gamma production by cultured spleen cells. By 34 wk postinfection, there was an abrupt cessation of IFN-gamma production. No IL-4 was detected, ruling out a switch to Th2 profile. Subsequently, bacterial numbers increased still further to >5 x 109 per lung, and the mice lost body weight and would have died if not killed for experimental or humane reasons. The possibility that T cells exposed over this prolonged period to extremely high doses of Ag may become tolerant by a process of terminal differentiation is discussed.

This publication has 0 references indexed in Scilit: