TY - JOUR
T1 - Resident lung antigen-presenting cells have the capacity to promote Th2 T cell differentiation in situ
AU - Constant, Stephanie L.
AU - Brogdon, Jennifer L.
AU - Piggott, Damani A.
AU - Herrick, Christina A.
AU - Visintin, Irene
AU - Ruddle, Nancy H.
AU - Bottomly, Kim
PY - 2002/11
Y1 - 2002/11
N2 - 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 CD11cbright 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.
AB - 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 CD11cbright 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.
UR - http://www.scopus.com/inward/record.url?scp=0036853910&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036853910&partnerID=8YFLogxK
U2 - 10.1172/JCI0216109
DO - 10.1172/JCI0216109
M3 - Article
C2 - 12438442
AN - SCOPUS:0036853910
SN - 0021-9738
VL - 110
SP - 1441
EP - 1448
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 10
ER -