A complex of effector and predominant regulatory immune responses are induced in the female reproductive tract (FRT) due to insemination that is necessary to achieve pregnancy [1,2,3]. Semen is composed of seminal fluid, spermatozoa and non-spermatozoa cells which include round cells and immune cells [4]. Seminal fluid contains immune regulatory factors such as prostaglandins, transforming growth factor β (TGF-β), IL-10, and others [5]. In addition to seminal fluid immune regulatory factors, spermatozoa also express immune regulatory molecules. Human leukocyte antigen (HLA)-G [6], HLA-E [7], and Fas-ligand [8] are some examples of immunoregulatory molecules expressed by spermatozoa. The expression of such immune markers by spermatozoa indicates the significance of the interaction between spermatozoa and immune cells recruited to the FRT in the arrangement of proper immunity for pregnancy occurrence. It also raises the possibility of the presence of other immune molecules on spermatozoa. There is a variety of immune regulatory molecules such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1(PD1) and its ligand (PD-L1), T cell immunoglobulin mucin-3 (tim3) [9], and CD5 [10] whose expression by spermatozoa, to the best of our knowledge, has not yet been investigated.
Given the great importance of the regulatory immune response to spermatozoa for a successful pregnancy and the obvious relationship between the immune dysregulation in the FRT and pregnancy disorders [11], elucidation of the immune molecules expressed by spermatozoa is necessary. Expanding our knowledge about the molecules involved in reproductive immunity can empower us to propose therapeutic interventions in immune dysregulation.
Among the above mentioned molecules, CD5 has particular importance because of its specific impact on the survival and receptor signaling of T and B lymphocytes, being the central cells in immune reactions [12]. CD5 is a scavenger receptor that is expressed by lymphocytes, primarily thymocytes, mature T cells, a subset of B cells (in mice B1a cells), and also by dendritic cells which are interacting with lymphocytes [13]. CD5 has a functional role in immune tolerance, modulating T helper differentiation as well as Tregs and regulatory B cells (Breg) homeostasis [13]. For example, a high expression of CD5 on T cells results in the induction of Treg cells. In contrast, lack of CD5 on T cells is accompanied with elevated activation and increased “activation-induced cell death” and anergy [14]. Development and function of B1a cells is dependent on CD5 expression [13]. CD5-positive dendritic cells lead to decreased activation of CD4- and CD8-positive T cells [14]. Accordingly, we supposed that CD5 may be one of the immune molecules which is expressed by spermatozoa to regulate T and B cell penetration to the FRT following insemination. Therefore, the aim of this study is to investigate the expression of CD5 on the surface of human spermatozoa.