title: Th1-driven immune reconstitution disease in Mycobacterium avium-infected mice.
abstract: 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 interferonγ 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.
authors.affiliation: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA. barberd@niaid.nih.gov
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Barber
authors.forename: Katrin D
authors.initials: KD
authors.lastname: Mayer-Barber
authors.forename: Lis R V
authors.initials: LR
authors.lastname: Antonelli
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wilson
authors.forename: Sandra
authors.initials: S
authors.lastname: White
authors.forename: Patricia
authors.initials: P
authors.lastname: Caspar
authors.forename: Sara
authors.initials: S
authors.lastname: Hieny
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000209:etiology / Q000276:immunology* / Q000382:microbiology* / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D009162:Mycobacterium avium / Q000276:immunology* / Q000302:isolation & purification; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D014376:Tuberculosis / Q000150:complications*; D015431:Weight Loss
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines