Abstract
The immune system plays an important role in immunity (immune surveillance), but also in the regulation of tissue homeostasis (immune physiology). Lessons from the female reproductive tract indicate that immune system related cells, such as intraepithelial T cells and monocyte-derived cells (MDC) in stratified epithelium, interact amongst themselves and degenerate whereas epithelial cells proliferate and differentiate. In adult ovaries, MDC and T cells are present during oocyte renewal from ovarian stem cells. Activated MDC are also associated with follicular development and atresia, and corpus luteum differentiation. Corpus luteum demise resembles rejection of a graft since it is attended by a massive influx of MDC and T cells resulting in parenchymal and vascular regression. Vascular pericytes play important roles in immune physiology, and their activities (including secretion of the Thy-1 differentiation protein) can be regulated by vascular autonomic innervation. In tumors, MDC regulate proliferation of neoplastic cells and angiogenesis. Tumor infiltrating T cells die among malignant cells. Alterations of immune physiology can result in pathology, such as autoimmune, metabolic, and degenerative diseases, but also in infertility and intrauterine growth retardation, fetal morbidity and mortality. Animal experiments indicate that modification of tissue differentiation (retardation or acceleration) during immune adaptation can cause malfunction (persistent immaturity or premature aging) of such tissue during adulthood. Thus successful stem cell therapy will depend on immune physiology in targeted tissues. From this point of view, regenerative medicine is more likely to be successful in acute rather than chronic tissue disorders.
Highlights
More than eighty years ago, Alexis Carrel demonstrated that leukocyte extracts, like embryonic tissue extracts, stimulate multiplication of fibroblasts in vitro, and suggested that leukocytes can bring growth-activating substances to tissue-specific cells [1]
Similar emergence of secondary germ cells by asymmetric division of ovarian stem cells (OSC) triggered by monocyte derived cells (MDC) and T cells has been observed in adult human ovaries [35, 57] and expression of a meiosis marker, the meiotic entry synaptonemal complex protein-3 (SCP3), in segments of tunica albuginea and OSC, and in some oocytes of primordial follicles was detected in functional adult human and monkey ovaries [71]
Regarding the argument (B) that OSC are not essential for neo-oogenesis since the oocytes persist in ovaries lacking OSC, we recently demonstrated that in rat ovaries lacking OSC, the oocytes originate by an alternate pathway, from medullary somatic stem cells; primordial follicles are formed in the juxtaposed ovarian cortex [72]
Summary
More than eighty years ago, Alexis Carrel demonstrated that leukocyte extracts, like embryonic tissue extracts, stimulate multiplication of fibroblasts in vitro, and suggested that leukocytes can bring growth-activating substances to tissue-specific cells [1]. Secondary germ cells are formed in fetal and adult human ovaries by asymmetric division of OSC, with the assistance of MDC and T cells [35, 36, 57].
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