TY - JOUR
T1 - Regulation of contact hypersensitivity by interleukin 10
AU - Ferguson, Thomas A.
AU - Dube, Philip
AU - Griffith, Thomas S.
PY - 1994/5/1
Y1 - 1994/5/1
N2 - Contact hypersensitivity (CHS) responses require the participation of T cells, along with a variety of cytokines and adhesion molecules. In the classical CHS, antigen-specific T cells are recruited to a site of antigenic challenge, where they react with antigen, release cytokines, and attract other inflammatory cells. In the mouse model of CHS, this reaction is elicited in sensitized mice by application of the immunogen 4-7 d after immunization. The reaction peaks at 24 h, is slightly reduced by 48 h, and can return to normal by 72 h. This is in spite of the fact that some antigen is still present at the site of challenge. Here we examined the hypothesis that locally produced interleukin 10 (IL-10) regulates the duration of the response. Our data show that IL-10 protein peaked 10-14 h after antigenic challenge and returned to background by 24 h. The production of IL-10 protein corresponded with, and followed IL-10 mRNA transcription as detected by reverse transcriptase-polymerase chain reaction. During peak IL-10 production after antigenic challenge, it was not possible to transfer CHS with immune lymphoid cells, unless neutralizing antibody to IL-10 was given first. Additionally, when sensitized mice were given neutralizing anti-IL-10 antibody at the time of antigenic challenge, the duration of CHS was prolonged well beyond the natural course of the response. Finally, we demonstrate that rIL-10, when injected into the skin before antigenic challenge, prevented the elicitation of CHS in previously sensitized mice. Taken together, our data show an important role for IL-10 in the natural regulation of CHS responses in vivo.
AB - Contact hypersensitivity (CHS) responses require the participation of T cells, along with a variety of cytokines and adhesion molecules. In the classical CHS, antigen-specific T cells are recruited to a site of antigenic challenge, where they react with antigen, release cytokines, and attract other inflammatory cells. In the mouse model of CHS, this reaction is elicited in sensitized mice by application of the immunogen 4-7 d after immunization. The reaction peaks at 24 h, is slightly reduced by 48 h, and can return to normal by 72 h. This is in spite of the fact that some antigen is still present at the site of challenge. Here we examined the hypothesis that locally produced interleukin 10 (IL-10) regulates the duration of the response. Our data show that IL-10 protein peaked 10-14 h after antigenic challenge and returned to background by 24 h. The production of IL-10 protein corresponded with, and followed IL-10 mRNA transcription as detected by reverse transcriptase-polymerase chain reaction. During peak IL-10 production after antigenic challenge, it was not possible to transfer CHS with immune lymphoid cells, unless neutralizing antibody to IL-10 was given first. Additionally, when sensitized mice were given neutralizing anti-IL-10 antibody at the time of antigenic challenge, the duration of CHS was prolonged well beyond the natural course of the response. Finally, we demonstrate that rIL-10, when injected into the skin before antigenic challenge, prevented the elicitation of CHS in previously sensitized mice. Taken together, our data show an important role for IL-10 in the natural regulation of CHS responses in vivo.
UR - http://www.scopus.com/inward/record.url?scp=0028226996&partnerID=8YFLogxK
U2 - 10.1084/jem.179.5.1597
DO - 10.1084/jem.179.5.1597
M3 - Article
C2 - 8163939
AN - SCOPUS:0028226996
SN - 0022-1007
VL - 179
SP - 1597
EP - 1604
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 5
ER -