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

Barber DL, Mayer-Barber KD, Antonelli LR, Wilson MS, White S, Caspar P, Hieny S, Sereti I, Sher A.

Blood. 2010 Nov 4;116(18):3485-93. doi: 10.1182/blood-2010-05-286336. Epub 2010 Jul 23.

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.

PMID: 20656932

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.