Th1-driven immune reconstitution disease in Mycobacterium avium-infected mice.
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.
Barber
Daniel L
DL
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
Mayer-Barber
Katrin D
KD
Antonelli
Lis R V
LR
Wilson
Mark S
MS
White
Sandra
S
Caspar
Patricia
P
Hieny
Sara
S
Sereti
Irini
I
Sher
Alan
A
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
D000942:Antigens, Bacterial; D016207:Cytokines