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Publication : Th1-driven immune reconstitution disease in Mycobacterium avium-infected mice.

First Author  Barber DL Year  2010
Journal  Blood Volume  116
Issue  18 Pages  3485-93
PubMed ID  20656932 Mgi Jnum  J:166473
Mgi Id  MGI:4845817 Doi  10.1182/blood-2010-05-286336
Citation  Barber DL, et al. (2010) Th1-driven immune reconstitution disease in Mycobacterium avium-infected mice. Blood 116(18):3485-93
abstractText  Following antiretroviral therapy, a significant proportion of HIV(+) patients with mycobacterial coinfections develop a paradoxical, poorly understood inflammatory disease termed immune reconstitution inflammatory syndrome (IRIS). Here, we show that Mycobacterium avium-infected T cell-deficient mice injected with CD4 T cells also develop an immune reconstitution disease (IRD) manifesting as weight loss, impaired lung function, and rapid mortality. This form of IRD requires Ag recognition and interferongamma production by the donor CD4 T cells and correlates with marked alterations in blood and tissue CD11b(+) myeloid cells. Interestingly, disease is associated with impaired, rather than augmented, T-cell expansion and function and is not strictly dependent on lymphopenia-induced T-cell proliferation. Instead, our findings suggest that mycobacterial-associated IRIS results from a heightened sensitivity of infected lymphopenic hosts to the detrimental effects of Ag-driven CD4 T-cell responses.
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