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Intravenous Ig therapy (IVIg) is reported to be a useful regimen in treating autoimmune diseases. In this study, we asked whether IVIg (in vitro) could increase the expression of TGF-β, IL-10, and the transcription factor FoxP3 in T regulatory (Treg) cells, and the idea that IVIg could enhance suppressive properties of these cells. CD4+ T cells from 12 healthy individuals were cultured in the presence or absence of IVIg vs human control IgG during 16, 24, and 36 h. Using FACS analysis and gating on CD4+CD25high Treg cells, we assessed the expression of intracellular TGF-β, IL-10, and FoxP3. In addition, the production of TNF-α by stimulated CD4+ T cells alone or in culture with CD25+ by itself or together with IVIg was also assessed. The presence of IVIg with Treg cells in culture significantly increased the intracellular expression of TGF-β (17.7 ± 8.5% vs 29.8 ± 13%; p = 0.02), IL-10 (20.7 ± 4.7% vs 34.2 ± 5.2%; p = 0.008) and FoxP3 (20.8 ± 5.2% vs 33.7 ± 5.9%; p = 0.0006) when compared with cells cultured alone or with control human IgG. The suppressive effect of CD4+CD25+ T cells presented as the decrease of TNF-α production by stimulated CD4+CD25− (effector T cells) was further increased by adding IVIg to cell culture. We hereby demonstrate an additional mechanism by which IVIg could maintain self-tolerance and decrease immune-mediated inflammation.

INTRODUCTION:To investigate whether immunologic factors in breast milk change in response to nursing infants' infection. RESULTS: Total cD45 leukocyte count dropped from 5,655 (median and interquartile range: 1,911; 16,871) in the acute phase to 2,122 (672; 6,819) cells/ml milk after recovery with macrophage count decreasing from 1,220 (236; 3,973) to 300 (122; 945) cells/ml. Tumor necrosis factor-α (TNFα) levels decreased from 3.66 ± 1.68 to 2.91 ± 1.51 pg/ml. The decrease in lactoferrin levels was of borderline statistical significance. such differences were not recorded in samples of the controls. Interleukin-10 levels decreased in the sick infants' breast milk after recovery, but also in the healthy controls, requiring further investigation. secretory immunoglobulin a levels did not change significantly in the study or control group. DISCUSSION: During active infection in nursing infants, the total number of white blood cells, specifically the number of macrophages, and TNFα levels increase in their mothers' breast milk. These results may support the dynamic nature of the immune defense provided by breastfeeding sick infants. METHODS: Breast milk from mothers of 31 infants, up to 3 months of age, who were hospitalized with fever, was sampled during active illness and recovery. Milk from mothers of 20 healthy infants served as controls.T he increased sensitivity of the newborn infant to infections originates from the immaturity of the immune system (1). In addition to transfer of immunoglobulin G to the fetus through the placenta, breastfeeding constitutes an important immunological support that the mammalian mother can provide to her relatively immunocompromised offspring against infections during the first months of life (2-6). The immune system in human milk includes secretory immunoglobulin A (sIgA), immunoglobulin G, free fatty acids, monoglycerides, proteins such as lactoferrin, lactalbumin, glycans, nonabsorbed oligosaccharides, exosomes, immunomodulators such as cytokines, nucleic acids, antioxidants, and immune cells such as macrophages, neutrophils, and lymphocytes (1,4,5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). All these immunologic milk constituents interact together and with the newborn's gut directly or indirectly (e.g., by changing the gut flora) to increase immunity against infection, and probably also contribute to the maturation and efficiency of the newborn immune system (5,6).Many studies in both industrialized and developing countries have shown that nursing infants are less vulnerable to infections during their first months of life, including gastroenteritis, respiratory infections, otitis media, urinary tract infections, and necrotizing enterocolitis in premature infants (3,(18)(19)(20)(21)(22)(23)(24)(25).The mechanisms involved in the immunity provided by human milk to the nursing infant are not fully understood. Until recently, it was believed that the changes in immunological constituents of breast milk were mostly related to the time that elapsed from delivery or, in some cases,...

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IVIg attenuates the activation of TLR-9 in B cells from SLE patients, suggesting a novel additional mechanism of IVIg mode of action in these patients.

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