Interleukin-2 and loss of immunity in experimental Mycobacterium avium infection.
Experimental infection of mice with a virulent strain of Mycobacterium avium leads to a slowly progressive disease, which we have previously shown culminates in loss of gamma interferon (IFN-gamma) 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 throughout M. avium infection 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-2Ralpha) 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-gamma production.
Mannering
Stuart I
SI
Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia. mannering@wehi.edu.au
Cheers
Christina
C
D000818:Animals; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002455:Cell Division; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007376:Interleukin-2 / Q000276:immunology*; D019041:L-Selectin / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D015269:Mycobacterium avium Complex / Q000254:growth & development / Q000276:immunology; D015270:Mycobacterium avium-intracellulare Infection / Q000276:immunology* / Q000382:microbiology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D015415:Biomarkers; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D019041:L-Selectin