BACKGROUND: Untreated, more than 95% of female SWR x NZB: F(1) (SNF(1)) mice spontaneously develop a fatal lupus-like glomerulonephritis by 8 months-of-age, while disease onset in males is much slower. METHODS: : Timed-pregnant SNF(1) mice (10 per treatment) were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gestational day (GD) 12 by oral maternal gavage with 0, 40, or 80 microg/kg TCDD. RESULTS: Offspring of the TCDD-exposed dams showed numerous alterations in T lineage cells at 24 weeks-of-age. Females but not males showed decreased CD4(+)8(+) and increased CD4(-)8(-) thymocytes. Females also showed increased autoreactive CD4(+)Vbeta17(a+) axillary and inguinal lymph node T cells. Concanavalin A-stimulated splenocytes from prenatal TCDD-treated mice produced decreased interleukin 17 (IL-17) in the females while males showed increased IL-2 and IFN-gamma, and diminished IL-4. Mitogen-stimulated pan-lymphoproliferative responses were significantly increased across sex by TCDD. Anti-IgG and anti-C3 immune complex deposition in kidneys was present in the males after TCDD, and visibly worsened in females. CONCLUSIONS: Developmental TCDD exposure can permanently alter T lymphopoiesis in autoimmune-prone SNF1 mice. The alteration profile is beyond the classic immune suppression response, to also include exacerbation and induction of a lupuslike autoimmune disease.
BACKGROUND: Untreated, more than 95% of female SWR x NZB: F(1) (SNF(1)) mice spontaneously develop a fatal lupus-like glomerulonephritis by 8 months-of-age, while disease onset in males is much slower. METHODS: : Timed-pregnant SNF(1) mice (10 per treatment) were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gestational day (GD) 12 by oral maternal gavage with 0, 40, or 80 microg/kg TCDD. RESULTS: Offspring of the TCDD-exposed dams showed numerous alterations in T lineage cells at 24 weeks-of-age. Females but not males showed decreased CD4(+)8(+) and increased CD4(-)8(-) thymocytes. Females also showed increased autoreactive CD4(+)Vbeta17(a+) axillary and inguinal lymph node T cells. Concanavalin A-stimulated splenocytes from prenatal TCDD-treated mice produced decreased interleukin 17 (IL-17) in the females while males showed increased IL-2 and IFN-gamma, and diminished IL-4. Mitogen-stimulated pan-lymphoproliferative responses were significantly increased across sex by TCDD. Anti-IgG and anti-C3 immune complex deposition in kidneys was present in the males after TCDD, and visibly worsened in females. CONCLUSIONS: Developmental TCDD exposure can permanently alter T lymphopoiesis in autoimmune-prone SNF1 mice. The alteration profile is beyond the classic immune suppression response, to also include exacerbation and induction of a lupuslike autoimmune disease.
Authors: Zhinan Yin; Gul Bahtiyar; Na Zhang; Lanzhen Liu; Ping Zhu; Marie E Robert; Jennifer McNiff; Michael P Madaio; Joe Craft Journal: J Immunol Date: 2002-08-15 Impact factor: 5.422