Abstract
Mice expressed for 20 min daily to aerosolized ovalbumin (OVA) for 10 d at concentrations from 1 to 0.01% OVA made greatly reduced immunoglobulin (Ig)-E responses to subsequent immunogenic OVA challenges, given either intraperitoneally or aerosol. This IgE-specific unresponsiveness lasted for at least four months. However, these aerosol-treated mice were primed for larger OVA-specific IgG1 and IgG2a responses. The specific reduction in IgE responses was not due to preferential induction of a T helper (Th)-1 response as aerosol OVA-primed mice made greatly reduced Th2 and no detectable Th1 response after rechallenge in vitro. Consistent with this, the increase in circulating eosinophils observed in control Th2-primed mice was absent in aerosol OVA-treated animals. Interferon (IFN)-γ was not required for this unresponsiveness, as IFN-γ knockout mice and anti-IFN-γ antibody-treated wild type mice had greatly reduced levels of IgE similar to wild-type controls. CD8+ T cells played a relatively small role as IgE responses were reduced to about the same extent in β2 microglobulin-deficient, or in anti- CD8-treated wild-type mice as in normal mice after aerosol OVA treatment. Similarly, T cell receptor (TCR)-γ/δ T cells were not required for maximal inhibition of the IgE response. These results demonstrate that exposure to inhaled protein antigens can induce a state of unresponsiveness of CD4+ T cells that results in a prolonged loss of IgE and eosinophil responses to subsequent challenges. This T cell unresponsiveness was shown not to require CD8+ or TCR-γ/δ+ T cells or IFN-γ.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 721-731 |
| Number of pages | 11 |
| Journal | Journal of Experimental Medicine |
| Volume | 187 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 2 1998 |
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ASJC Scopus subject areas
- Immunology
Cite this
Aerosol-induced immunoglobulin (Ig)-E unresponsiveness to ovalbumin does not require CD8+ or T cell receptor (TCR)-γ/δ+ T cells or interferon (IFN)-γ in a murine model of allergen sensitization. / Seymour, Brian W P; Gershwin, Laurel J; Coffman, Robert L.
In: Journal of Experimental Medicine, Vol. 187, No. 5, 02.03.1998, p. 721-731.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Aerosol-induced immunoglobulin (Ig)-E unresponsiveness to ovalbumin does not require CD8+ or T cell receptor (TCR)-γ/δ+ T cells or interferon (IFN)-γ in a murine model of allergen sensitization
AU - Seymour, Brian W P
AU - Gershwin, Laurel J
AU - Coffman, Robert L.
PY - 1998/3/2
Y1 - 1998/3/2
N2 - Mice expressed for 20 min daily to aerosolized ovalbumin (OVA) for 10 d at concentrations from 1 to 0.01% OVA made greatly reduced immunoglobulin (Ig)-E responses to subsequent immunogenic OVA challenges, given either intraperitoneally or aerosol. This IgE-specific unresponsiveness lasted for at least four months. However, these aerosol-treated mice were primed for larger OVA-specific IgG1 and IgG2a responses. The specific reduction in IgE responses was not due to preferential induction of a T helper (Th)-1 response as aerosol OVA-primed mice made greatly reduced Th2 and no detectable Th1 response after rechallenge in vitro. Consistent with this, the increase in circulating eosinophils observed in control Th2-primed mice was absent in aerosol OVA-treated animals. Interferon (IFN)-γ was not required for this unresponsiveness, as IFN-γ knockout mice and anti-IFN-γ antibody-treated wild type mice had greatly reduced levels of IgE similar to wild-type controls. CD8+ T cells played a relatively small role as IgE responses were reduced to about the same extent in β2 microglobulin-deficient, or in anti- CD8-treated wild-type mice as in normal mice after aerosol OVA treatment. Similarly, T cell receptor (TCR)-γ/δ T cells were not required for maximal inhibition of the IgE response. These results demonstrate that exposure to inhaled protein antigens can induce a state of unresponsiveness of CD4+ T cells that results in a prolonged loss of IgE and eosinophil responses to subsequent challenges. This T cell unresponsiveness was shown not to require CD8+ or TCR-γ/δ+ T cells or IFN-γ.
AB - Mice expressed for 20 min daily to aerosolized ovalbumin (OVA) for 10 d at concentrations from 1 to 0.01% OVA made greatly reduced immunoglobulin (Ig)-E responses to subsequent immunogenic OVA challenges, given either intraperitoneally or aerosol. This IgE-specific unresponsiveness lasted for at least four months. However, these aerosol-treated mice were primed for larger OVA-specific IgG1 and IgG2a responses. The specific reduction in IgE responses was not due to preferential induction of a T helper (Th)-1 response as aerosol OVA-primed mice made greatly reduced Th2 and no detectable Th1 response after rechallenge in vitro. Consistent with this, the increase in circulating eosinophils observed in control Th2-primed mice was absent in aerosol OVA-treated animals. Interferon (IFN)-γ was not required for this unresponsiveness, as IFN-γ knockout mice and anti-IFN-γ antibody-treated wild type mice had greatly reduced levels of IgE similar to wild-type controls. CD8+ T cells played a relatively small role as IgE responses were reduced to about the same extent in β2 microglobulin-deficient, or in anti- CD8-treated wild-type mice as in normal mice after aerosol OVA treatment. Similarly, T cell receptor (TCR)-γ/δ T cells were not required for maximal inhibition of the IgE response. These results demonstrate that exposure to inhaled protein antigens can induce a state of unresponsiveness of CD4+ T cells that results in a prolonged loss of IgE and eosinophil responses to subsequent challenges. This T cell unresponsiveness was shown not to require CD8+ or TCR-γ/δ+ T cells or IFN-γ.
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UR - http://www.scopus.com/inward/citedby.url?scp=0032473551&partnerID=8YFLogxK
U2 - 10.1084/jem.187.5.721
DO - 10.1084/jem.187.5.721
M3 - Article
C2 - 9480982
AN - SCOPUS:0032473551
VL - 187
SP - 721
EP - 731
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 5
ER -