Temporal-spatial analysis of the immune response in a murine model of ovalbumin-induced airways inflammation.
The objective of this study was to define phenotypic changes of antigen-presenting cells (APCs) and T cells in a murine model of antigen-induced airways inflammation that involves intraperitoneal sensitization with ovalbumin (OVA)/adjuvant followed by antigen aerosolization. We investigated the APC and T-cell compartments both after sensitization (primary immune response) and after challenge (secondary immune response) at the thoracic lymph nodes (initiation site) and the lung (effector site). Our findings document a major cellular expansion in the lymph nodes after both sensitization and challenge. After sensitization, this expansion was comprised mainly of B cells, a considerable proportion of which expressed B7.2. At this time, T cells were markedly expanded and activated as assessed by CD69 expression; further, although GATA-3 and signal transducer and activator of transcription-6 were expressed at this time point, expression of interleukin (IL)-4, IL-5, and IL-13 messenger RNA (mRNA) levels were marginal. However, in vitro stimulation of lymph-node cells with OVA led to cytokine production. In contrast, 24 h after challenge, but not after sensitization, there was a major expansion of dendritic cells and macrophages in the lungs. This expansion was associated with enhanced expression of both B7.1 and B7.2. We also observed expansion of activated CD3(+)/CD4(+) T cells expressing the T helper-2-associated marker T1/ST2 in the lung, most notably 5 d after challenge. Further, IL-4, IL-5, and IL-13, but not interferon-gamma mRNA were expressed at high levels 3 h after challenge. This study helps to elucidate the "geography" of immune responses generated in a conventional murine model of allergic airways inflammation.
Gajewska
B U
BU
Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
Swirski
F K
FK
Alvarez
D
D
Ritz
S A
SA
Goncharova
S
S
Cundall
M
M
Snider
D P
DP
Coyle
A J
AJ
Gutierrez-Ramos
J C
JC
Stämpfli
M R
MR
Jordana
M
M
D000336:Aerosols; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D001985:Bronchial Provocation Tests; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008168:Lung / Q000166:cytology; D008198:Lymph Nodes / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin; D050800:STAT6 Transcription Factor; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D000336:Aerosols; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D000949:Histocompatibility Antigens Class II; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011506:Proteins; D018123:Receptors, Interleukin; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D010047:Ovalbumin