Interleukin-2 and Loss of Immunity in ExperimentalMycobacterium aviumInfection

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Abstract
Experimental infection of mice with a virulent strain ofMycobacterium aviumleads to a slowly progressive disease, which we have previously shown culminates in loss of gamma interferon (IFN-γ) production by T lymphocytes and death of the animals approximately 40 weeks after infection. Here we investigated the changes in T-cell activation, the production of interleukin-2 (IL-2), and the response to IL-2 throughoutM. aviuminfection as a possible explanation for this loss. We found that there is a steady increase in the percentage of T cells expressing activation markers right to the end of infection. However, in vivo T-cell proliferation, measured as a percentage of CD4+and CD8+cells incorporating 5-bromo-2′-deoxyuridine, initially increased but then remained constant. In the final stages of infection there was a decline in proliferation of activated (CD62L−) T cells. Since IL-2 is a major driver of T-cell proliferation, we asked whether this was due to loss of IL-2 responsiveness or production. However, CD25 (IL-2Rα) continued to be highly expressed in the terminal stages of infection, and although IL-2 production declined, addition of recombinant IL-2 to cultures could not rescue the final loss of IFN-γ production.