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Equine May/June 2007 (Vol 2, No 3)

Abstract Thoughts—Protecting Against Disease: What's a Mother to Do?

by David J. Hurley, PhD, James N. Moore, DVM, PhD

    Nelson JL, Gillespie KM, Lambert NC, et al: Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet beta cell microchimerism. Proc Natl Acad Sci 104(5):1637-1642, 2007.

    Abstract: Maternal cells have recently been found in the circulation and tissues of immune-competent children and adults. This is referred to as maternal microchimerism (MMc). Whether MMc confers benefits during development or later in life or sometimes has adverse effects is unknown. Type 1 diabetes is an autoimmune disease that primarily affects children and young adults. To identify and quantify MMc, we developed a panel of quantitative polymerase chain reaction assays that target nontransmitted, nonshared, maternal-specific human leukocyte antigen alleles. MMc was assayed in peripheral blood from 172 individuals—94 with type 1 diabetes, 54 unaffected siblings, and 24 unrelated healthy subjects. MMc levels, expressed as the genome equivalent per 100,000 proband cells, were significantly higher in patients with type 1 diabetes than in unaffected siblings and healthy subjects; the medians were 0.09 (range: 0 to 530), 0 (range: 0 to 153), and 0 (range: 0 to 7.9), respectively. Differences between groups were evident irrespective of human leukocyte antigen genotypes. However, in patients with the type 1 diabetes-associated DQB1*0302-DRB1*04 haplotype, MMc was found more often when the haplotype was paternally (70%) rather than maternally (14%) transmitted. In other studies, we looked for female islet beta cells in four pancreases obtained from autopsies of male subjects (one from a patient with type 1 diabetes) using fluorescent in situ hybridization for X and Y chromosomes with concomitant CD45 and beta cell insulin staining. Female islet beta cells (presumed maternal) formed 0.39% to 0.96% of the total, whereas female hematopoietic cells were very rare. Thus patients with type 1 diabetes have higher levels of MMc in their circulation than do unaffected siblings and healthy individuals, and MMc contributes to islet beta cells in progeny.

    This abstract has been adapted with permission. Copyright 2007 National Academy of Sciences, USA.

    Commentary: There is nothing like a mother's love. Mother's overriding goal is to protect her offspring from evil, danger, dirt, and even ourselves. Early on, she was on the lookout for bullies; then she covered her eyes at high school football games and stayed up until we returned from a (party, Grateful Dead concert, ski trip, parole meeting [select one]), just to be sure we were all right. However, it appears that there are even more intimate forms of motherly love, one of which is addressed in the article by Nelson and coworkers abstracted above. This article provides evidence that maternal stem cells that are transferred to offspring, either before birth or with colostrum, appear to monitor the well-being of the offspring and attempt to cover their weaknesses. For example, in this comparison of two groups of boys, one with type 1 diabetes and one without the disease, the number of circulating maternal cells was clearly higher in the diabetic children than in their healthy siblings. Furthermore, a significantly higher number of female beta cells was present among the pancreatic islet (beta) cells in the diabetic boys who died than in the boys who died from unrelated conditions.

    One of us (DH) has studied the transfer of maternal cells to the neonate via colostrum for almost 25 years. We1 and others2-5 have shown that maternal cells cross the intestine, traffic in the circulation, and, after about 30 to 48 hours, find their way to mucosal and secondary lymphoid tissues. Collectively, these studies have shown that maternal cells in 1- and 2-day-old neonates respond to viral antigens,6 enhance antigen presentation and alloantigen recognition, generate tolerance to maternal major histocompatibility antigens,7 and alter the neonate's responses to bacteria.8

    Like calves and piglets, foals depend highly on the transfer of colostrum for neonatal immune protection. The colostrum they receive is rich in cells, cytokines, growth factors, antibodies, and nutrients. We believe that foals, like calves, lambs, and piglets, have a mechanism that allows maternal cells to enter and circulate shortly after birth, although this has not been definitively demonstrated. Furthermore, it is highly likely that those maternal cells go to many different tissues and monitor the well-being of the foal, possibly for a long time, much as Nelson and coworkers have shown occurs in humans.

    What does all this mean? First, it is one more reason that foals must receive good-quality colostrum as early as possible after birth and in a significant quantity. Second, it means that good-quality colostrum can no longer be defined based only on the amount of antibody transferred. Third, it means that colostrum replacements, although clearly better than nontransference of antibodies, fall short of providing immunologic protection like mother makes!

    Finally, it means that Frank Zappa was right when he said,

    Motherly love

    Motherly love

    Forget about

    The brotherly and otherly love

    Motherly love

    Is just the thing for you

    You know your mother's gonna love ya

    'Til ya don't know what to do

    Freakout, 1966

    1. Reber AJ, Hippen AR, Hurley DJ: Colostrum induced phenotypic and trafficking changes in maternal mononuclear cells in a peripheral blood leukocyte model for study of leukocyte transfer to the neonatal calf. Am J Vet Res 109:139-150, 2006.

    2. Williams PP: Immunomodulating effects of intestinal absorbed maternal colostral leukocytes by neonatal pigs. Can J Vet Res 57:1-8, 1993.

    3. Schnorr KL, Pearson LD: Intestinal absorption of maternal leukocytes by newborn lambs. J Reprod Immunol 6:329-337, 1984.

    4. Sheldrake RF, Husband AJ: Intestinal uptake of intact maternal lymphocytes by neonatal rats and lambs. Res Vet Sci 39:10-15, 1985.

    5. Tuboly S, Bernath S, Glavitis R, Medveczky I: Intestinal absorption of colostral lymphoid cells in newborn piglets. Vet Immunol Immunopathol 20:75-85, 1988.

    6. Donovan DC, Reber AJ, Gabbard JS, et al: Impact of maternal cells transferred with colostrum on cellular responses to pathogen antigens in neonatal calves. Am J Vet Res, accepted for publication, 2007.

    7. Reber AJ, Hippen AR, Hurley DJ: Effects of the ingestion of whole colostrum or cell-free colostrum on the capacity of leukocytes in newborn calves to stimulate or respond in one-way mixed leukocyte cultures. Am J Vet Res 66:1854-1860, 2005.

    8. Riedel-Caspari G, Schmidt FW: The influence of colostral leukocytes on the immune system of the neonatal calf. I. Effects on lymphocyte responses. Dtsch Tierarztl Wochenschr 98:102-107, 1991.

    References »

    NEXT: Clinical Snapshot (June 2007)

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