Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring

Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue

A polymeric IgA response in serum can be produced by parenteral immunization.

The magnitude and the kinetics of the serum-specific polymeric (p-) and monomeric (m-) IgA antibody responses were analysed following parenteral stimulation with tetanus toxoid (TT) vaccine in 10 volunteers, 5-20 years after a previous boost. A rapid marked serum IgA antibody response involving both the monomeric and polymeric components of IgA was observed: m-IgA and p-IgA antibodies reached a peak of serum activity at about 11 days, around 6 days before the peak of IgG antibody activity. At the peak of the IgA response, p-IgA accounted for approximately half of the anti-TT activity (median 54%, 25-79%). However, p-IgA antibodies rapidly disappeared from serum over a few weeks, whereas the serum m-IgA antibody response was maintained over a prolonged period of time. For one subject out of five, anti-TT IgA were also detected in saliva with a peak of activity earlier than in serum. Calculation of the albumin relative coefficient of excretion for anti-TT IgA in this saliva suggested a local synthesis of these antibodies. The present study indicates that a polymeric IgA antibody response in serum can be produced by parenteral immunization in primed individuals, and it raises the question of the mechanisms that control polymeric versus monomeric IgA production

Genetic deficiency of C4, C2 or C1q and lupus syndromes. Association with anti-Ro (SS-A) antibodies.

Sera from 15 patients with genetically determined complement component deficiencies were studied for the presence of antibodies to various nuclear antigens. One of three patients with C2 deficiency presented with systemic lupus erythematosus (SLE); all eight patients with C4 deficiency had either SLE or a lupus-like syndrome, and two of four patients with functional C1q deficiency had SLE. Five of nine complement deficiency patients with SLE studied had measurable antinuclear antibody titres, but only two had antibodies against native DNA. Precipitating antibodies against extractable nuclear antigens were found in sera from seven of the 11 complement deficient patients with SLE; one had only antibodies against antigens extracted from calf thymus (ECT), six patients (one with C2 deficiency, four with C4 deficiency and one with C1q deficiency) had anti-Ro (SS-A) antibodies with or without anti-ECT antibodies. The frequency of anti-Ro antibodies in the complement deficient population with SLE (55%) was significantly higher (P less than 0.02) than that of a control population of SLE patients without genetically determined complement deficiencies (27%)

Kinetics of anti-Campylobacter jejuni monomeric and polymeric immunoglobulin A1 and A2 responses in serum during acute enteritis.

The intensity and kinetics of the serum polymeric and monomeric immunoglobulin A1 (IgA1) and IgA2 antibody responses to Campylobacter jejuni were analyzed. A rapid and marked serum IgA antibody response involving both the monomeric and polymeric components of IgA was observed after C. jejuni infections. IgA antibodies reached a peak of activity in serum during week 2 after the first symptoms of enteritis, about 10 days before the peak of IgG activity. Polymeric IgA accounted for most of the anti-C. jejuni activity at the peak of the IgA response (median, 90%; range, 44 to 98%) but rapidly disappeared from serum over a few weeks. In contrast, the serum monomeric IgA antibody response was low and was maintained over a prolonged period of time. Anti-C. jejuni IgA detected in the serum of healthy blood donors was mainly monomeric (median, 83%; range, 17 to 94%). In both the patients and the positive controls, IgA1 was the predominant (greater than 85%) subclass involved, even when the IgA antibody response was mainly polymeric. Our results suggest that polymeric IgA antibody responses are linked to a strong or persisting antigenic stimulation or both. Polymeric IgA antibodies appear to be a potential marker of acute C. jejuni infections, and their determination could provide a useful tool for the serological diagnosis of recent C. jejuni infections