Resident lung antigen-presenting cells have the capacity to promote Th2 T cell differentiation in situ.
Antigen exposure via airway epithelia is often associated with a failure to prime or with the preferential priming of Th2 cells. We previously reported that the intranasal delivery of a Th1-inducing antigen promoted Th2-dominated responses, rather than the expected Th1 responses. Thus, we proposed that when pulmonary T cell priming is induced, the lung microenvironment might intrinsically favor the generation of Th2 types of responses. To establish a potential mechanism for such preferential priming, we examined the initial interactions between antigens and resident antigen-presenting cells (APCs) within the lung. We show that intranasally delivered antigens are preferentially taken up and can be presented to antigen-specific T cells by a resident population of CD11c(bright) APCs. Most of these antigen-loaded APCs remained within lung tissues, and migration into secondary lymphoid organs was not crucial for T cell priming to occur within the pulmonary tract. Furthermore, these pulmonary APCs demonstrated a marked expression of IL-6 and IL-10 within hours of antigen uptake, suggesting that resident tissue APCs have the capacity to promote Th2 T cell differentiation in situ.
Constant
Stephanie L
SL
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA. mtmslc@gwumc.edu
Brogdon
Jennifer L
JL
Piggott
Damani A
DA
Herrick
Christina A
CA
Visintin
Irene
I
Ruddle
Nancy H
NH
Bottomly
Kim
K
D000281:Administration, Intranasal; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000953:Antigens, Protozoan / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002465:Cell Movement; D016207:Cytokines / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology; D008168:Lung / Q000166:cytology* / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology*
D000953:Antigens, Protozoan; D016207:Cytokines; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D016753:Interleukin-10