Intact NOX2 in T Cells Mediates Pregnancy-Induced Renal Damage in Dahl SS Rats

Area of Science:

• Reproductive biology and immunology
• Cardiovascular and renal physiology
• Oxidative stress mechanisms

Background:

• Hypertensive disorders of pregnancy increase risks for cardiovascular disease, renal disease, and mortality.
• The precise mechanisms are unclear, but T cells and reactive oxygen species are implicated.
• Dahl salt-sensitive (SS) rats, including T cell-deficient (SS^CD247-/-) and NOX2-deficient (SS^p67phox-/-) models, were used to study these mechanisms.

Purpose of the Study:

• To investigate the roles of T cells and NADPH oxidase 2 (NOX2) in pregnancy-induced renal damage and mortality.
• To determine if NOX2 specifically within T cells contributes to adverse pregnancy outcomes.
• To compare these effects in primigravida and multigravida states.

Main Methods:

• Assessed blood pressure and renal damage in SS, SS^CD247-/-, and SS^p67phox-/- rats during pregnancy.
• Performed adoptive transfers of splenocytes or CD4+ T cells from SS or SS^p67phox-/- donors into SS^CD247-/- recipients.
• Evaluated pregnancy-specific alterations in phenotype, including renal function and maternal mortality.

Main Results:

• Multigravida SS rats showed significant pregnancy-induced renal damage and mortality, which was reduced by deleting T cells or NOX2.
• Primigravida SS^p67phox-/- rats exhibited the greatest protection against renal damage.
• Adoptive transfer of SS splenocytes into SS^CD247-/- rats caused renal damage, while SS^p67phox-/- splenocytes did not; SS CD4+ T cells induced proteinuria and increased uterine artery resistance.

Conclusions:

• T cells and NOX2-derived reactive oxygen species contribute to end-organ damage in pregnancy.
• These factors increase maternal mortality in the SS rat model.
• Targeting T cells and NOX2 may offer protective strategies against pregnancy complications.