Cutting Edge: Ly49C/I− Neonatal NK Cells Predispose Newborns to Autoimmune Ovarian Disease Induced by Maternal Autoantibody

Abstract

NK cells are critical in immune responses against pathogens. However, their role in autoimmunity is still controversial. Here, we demonstrate that neonatal NK cells render newborns more susceptible to neonatal autoimmunity induced by maternal autoantibodies (nAOD); thus, neonatal but not adult NK cells are pathogenic after transfer into NK cell-deficient pups. The inhibitory receptors Ly49C/I are expressed in ~5% of neonatal and ~50% of adult NK cells. Here, we show that the presence of Ly49C/I+ adult NK cells inhibits nAOD induction. Thus, the ontogenetic regulation of Ly49C/I expression determines the propensity to autoantibody induced autoimmunity. In summary, our study provide definitive evidences of a pathogenic role of NK cells in neonatal autoimmunity and also elucidate a novel mechanism by which neonatal NK cells render newborns more susceptible to autoantibody induced autoimmunity.

Regulatory T Cells Control Th2-Dominant Murine Autoimmune Gastritis

“…As a positive control, we used the same IFN-γ antibody to block the development of neonatal autoimmune ovarian disease (nAOD) (45). nAOD was induced by intraperitoneal injection of 100μg of a monoclonal antibody (1G2 clone) to zona pellucida 3 peptide 336–342 on days 3 and 5 after birth (46), and anti-IFN-γ antibody was injected intraperitoneally every 3 to 4 days starting from postnatal day 3. Ovarian pathology was scored at 2 weeks of age as previously described (45).…”

Converting monoclonal antibody-based immunotherapies from passive to active: bringing immune complexes into play

“…Nevertheless, interactions between ICs and neonatal versus adult innate and adaptive immune systems still need to be investigated because mouse studies have revealed potential antibody-induced neonatal autoimmunity in certain settings. 85,86…”

Regulatory T-cells in Immune Tolerance and Organ-specific Autoimmunity

“…autoAb (229,372). We also found that NK and/or NKT cells were critical for juvenile AOD after Treg cell depletion.…”

“…For example, neonatal NK cells divide more rapidly than adult NK cells and predominantly express Ly49-inhibitory receptors. The Ly49-NK cell subset and production of IFN-γ are required for neonatal AOD and promote pathogenic neonatal T cell responses (229).…”

“…nAOD was induced by i.p. injection of 100 µg of a mAb (1G2 clone) to ZP3 peptide 336-342 on days 3 and 5 after birth(229), and anti-IFN-γ Ab was injected i.p. every 3-4 days starting from postnatal day 3.…”