Roles of IL-4 and IL-12 in the development of lupus in NZB/W F1 mice.
Development of either Th1 or Th2 cell subsets has profound immunologic consequences, either pathogenic or protective, in several autoimmune diseases. However, it remains unclear which subset of Th cells plays a more critical role in lupus. In this study, we examined IL-4 and IL-12, which play decisive roles in the development of Th2 and Th1, respectively, in the IgG autoantibody production and development of lupus nephritis in NZB/W (B/W) F1 mice. Transfer of either IL-4- or IL-12-stimulated splenocytes from 5-mo-old B/W F1 mice into B/W F1 mice of the same age enhanced the production of IgG anti-dsDNA Ab. Consistently, administration of mAb against either IL-4 or IL-12 before the onset of lupus could inhibit the production of IgG anti-dsDNA Ab. However, only anti-IL-4 mAb was effective in preventing the onset of lupus nephritis. This discrepancy appeared to be explained by the differential effect on the production of IgG3-type autoantibody and TNF production. Interestingly, when combined, anti-IL-12 mAb abrogated the beneficial effect of anti-IL-4 mAb. These results indicate that both Th2 and Th1 contribute to the IgG autoantibody production, and IL-4 and IL-12 play key roles in the complexity of cytokine regulation in the pathogenesis of autoimmunity in lupus, but the former is more critical.
Nakajima
A
A
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Hirose
S
S
Yagita
H
H
Okumura
K
K
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D005260:Female; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB; D011994:Recombinant Proteins; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E