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Role of inducible bronchus associated lymphoid tissue (iBALT) in respiratory immunity


Bronchus-associated lymphoid tissue (BALT) is occasionally found in the lungs of mice and humans; however, its role in respiratory immunity is unknown. Here we show that mice lacking spleen, lymph nodes and Peyer's patches generate unexpectedly robust primary B- and T-cell responses to influenza, which seem to be initiated at sites of induced BALT (iBALT). Areas of iBALT have distinct B-cell follicles and T-cell areas, and support T and B-cell proliferation. The homeostatic chemokines CXCL13 and CCL21 are expressed independently of TNFα and lymphotoxin at sites of iBALT formation. In addition, mice with iBALT, but lacking peripheral lymphoid organs, clear influenza infection and survive higher doses of virus than do normal mice, indicating that immune responses generated in iBALT are not only protective, but potentially less pathologic, than systemic immune responses. Thus, iBALT functions as an inducible secondary lymphoid tissue for respiratory immune responses.

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Figure 1: Influenza-specific CD8+ T cells are generated in mice lacking peripheral lymphoid organs.
Figure 2: Influenza-specific CD8+ effector T cells accumulate in the lungs of mice lacking peripheral lymphoid organs.
Figure 3: Influenza-specific IgG and germinal-center B cells are generated in mice lacking peripheral lymphoid organs.
Figure 4: iBALT is formed in influenza-infected SLP mice and supports T- and B-cell proliferation.
Figure 5: CXCL13 and CCL21 are induced in the lungs of influenza-infected mice and are found in areas of iBALT.
Figure 6: Viral clearance is slightly delayed in SLP mice, but survival is enhanced.


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This work was supported by Trudeau Institute and US National Institutes of Health grants HL69409 and HL63925 (T.D.R.), HL63925 and AI57158 (D.L.W.) and AI50844 and HL63925 (F.E.L.).

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Correspondence to Troy D Randall.

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Supplementary information

Supplementary Fig. 1

Generation of BM chimeric mice. (PDF 513 kb)

Supplementary Fig. 2

Splenectomized Rorγ−/− mice rapidly generate influenza-specific CD8 responses after infection. (PDF 72 kb)

Supplementary Fig. 3

Splenectomized Rorγ−/− mice rapidly generate influenza-specific antibody responses after infection. (PDF 42 kb)

Supplementary Fig. 4

Germinal center B cells are generated in mice lacking all peripheral lymphoid organs. (PDF 83 kb)

Supplementary Fig. 5

Expression of CXCL13 and CCL21 is induced in the lung after influenza infection. (PDF 394 kb)

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Moyron-Quiroz, J., Rangel-Moreno, J., Kusser, K. et al. Role of inducible bronchus associated lymphoid tissue (iBALT) in respiratory immunity. Nat Med 10, 927–934 (2004).

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