Abstract
A high-level expression of a transgene, Ea(d), encoding the I-E(d) α- chain is very effective in protection against murine lupus. To investigate the specific contribution of select H-2 haplotypes on the Ea(d) transgene- mediated disease-suppressing effect, we generated H-2 congenic (NZB x BXSB)F1 hybrid mice bearing either H-2(b/b), H-2(d/b), or H-2(d/d) haplotype, and compared the transgene-mediated protective effect on the clinical development (autoantibody production and glomerulonephritis) of lupus in these F1 hybrids. The level of protection was most remarkable in mice bearing the I-E- H-2(b/b) haplotype but was only minimal in I-E+ H- 2(d/d) F1 hybrids. Additional analysis demonstrated a marked suppression of lupus in I-E+ H-2(k/k) (MRL x BXSB)F1 hybrid mice, indicating that the transgene is able to suppress autoimmune responses even in mice already expressing I-E molecules at a homozygous level. Our results indicate that the level of the transgene-mediated protection is dependent on the host H-2 haplotype. This suggests that the autoimmune suppressive activity of the Ea(d) transgene is likely to be determined through the interaction of the transgene product with the host MHC class II molecules, providing new insight into the role of MHC in lupus-like autoimmunity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 505-511 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 164 |
| Issue number | 1 |
| State | Published - Jan 1 2000 |
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- Immunology
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Protection of murine lupus by the Ea(d) transgene is MHC haplotype- dependent. / Ibnou-Zekri, Nabila; Iwamoto, Masahiro; Gershwin, M. Eric; Izui, Shozo.
In: Journal of Immunology, Vol. 164, No. 1, 01.01.2000, p. 505-511.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Protection of murine lupus by the Ea(d) transgene is MHC haplotype- dependent
AU - Ibnou-Zekri, Nabila
AU - Iwamoto, Masahiro
AU - Gershwin, M. Eric
AU - Izui, Shozo
PY - 2000/1/1
Y1 - 2000/1/1
N2 - A high-level expression of a transgene, Ea(d), encoding the I-E(d) α- chain is very effective in protection against murine lupus. To investigate the specific contribution of select H-2 haplotypes on the Ea(d) transgene- mediated disease-suppressing effect, we generated H-2 congenic (NZB x BXSB)F1 hybrid mice bearing either H-2(b/b), H-2(d/b), or H-2(d/d) haplotype, and compared the transgene-mediated protective effect on the clinical development (autoantibody production and glomerulonephritis) of lupus in these F1 hybrids. The level of protection was most remarkable in mice bearing the I-E- H-2(b/b) haplotype but was only minimal in I-E+ H- 2(d/d) F1 hybrids. Additional analysis demonstrated a marked suppression of lupus in I-E+ H-2(k/k) (MRL x BXSB)F1 hybrid mice, indicating that the transgene is able to suppress autoimmune responses even in mice already expressing I-E molecules at a homozygous level. Our results indicate that the level of the transgene-mediated protection is dependent on the host H-2 haplotype. This suggests that the autoimmune suppressive activity of the Ea(d) transgene is likely to be determined through the interaction of the transgene product with the host MHC class II molecules, providing new insight into the role of MHC in lupus-like autoimmunity.
AB - A high-level expression of a transgene, Ea(d), encoding the I-E(d) α- chain is very effective in protection against murine lupus. To investigate the specific contribution of select H-2 haplotypes on the Ea(d) transgene- mediated disease-suppressing effect, we generated H-2 congenic (NZB x BXSB)F1 hybrid mice bearing either H-2(b/b), H-2(d/b), or H-2(d/d) haplotype, and compared the transgene-mediated protective effect on the clinical development (autoantibody production and glomerulonephritis) of lupus in these F1 hybrids. The level of protection was most remarkable in mice bearing the I-E- H-2(b/b) haplotype but was only minimal in I-E+ H- 2(d/d) F1 hybrids. Additional analysis demonstrated a marked suppression of lupus in I-E+ H-2(k/k) (MRL x BXSB)F1 hybrid mice, indicating that the transgene is able to suppress autoimmune responses even in mice already expressing I-E molecules at a homozygous level. Our results indicate that the level of the transgene-mediated protection is dependent on the host H-2 haplotype. This suggests that the autoimmune suppressive activity of the Ea(d) transgene is likely to be determined through the interaction of the transgene product with the host MHC class II molecules, providing new insight into the role of MHC in lupus-like autoimmunity.
UR - http://www.scopus.com/inward/record.url?scp=0033961825&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033961825&partnerID=8YFLogxK
M3 - Article
C2 - 10605048
AN - SCOPUS:0033961825
VL - 164
SP - 505
EP - 511
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -