Somatic-Immune Cells Crosstalk In-The-Making of Testicular Immune Privilege

Immunological infertility contributes significantly to the etiology of idiopathic male infertility. Shielding the spermatogenic cells from systemic immune responses is fundamental to secure normal production of spermatozoa. The body’s immune system is tuned with the host self-components since the early postnatal period, while sperm first develops during puberty, thus rendering spermatogenic proteins as ‘non-self’ or ‘antigenic.’ Development of antibodies to these antigens elicits autoimmune responses affecting sperm motility, functions, and fertility. Therefore, the testes need to establish a specialized immune-privileged microenvironment to protect the allogenic germ cells by orchestration of various testicular cells and resident immune cells. This is achieved through sequestration of antigenic germ cells by blood–testis barrier and actions of various endocrine, paracrine, immune-suppressive, and immunomodulatory mechanisms. The various mechanisms are very complex and need conceptual integration to disclose the exact physiological scenario, and to facilitate detection and management of immunogenic infertility caused by disruption of testicular immune regulation. The present review aims to (a) discuss the components of testicular immune privilege; (b) explain testicular somatic and immune cell interactions in establishing and maintaining the testicular immune micro-environment; and (c) illustrate the integration of multiple mechanisms involved in the control of immune privilege of the testis.