Little is known about autoreactive T cells in semen. Some studies provided evidence that their occurrence may be the consequence of immune reactions to prostatic antigens (autoimmune prostatitis). T cells proliferate in response to proteins of seminal plasma of men with autoimmune prostatitis [1, 3, 7]. Witkin and Goldstein [29] performed lymphocyte and monocyte counts in the semen of 14 men with intact vas deferens and 13 men who had undergone vasovasostotomy. In both groups, the number of lymphocytes and monocytes cells was identical with 10³/ml. However, in men with intact vasa, T suppressor/cytotoxic cells predominated. In contrast, in the vasovasostomized men, the levels of CD8+ T cells were significantly reduced and CD4+ T cells predominated in their semen. The authors thus speculated that damage to the excurrent ducts was responsible for the alteration in T cell regulation leading to a decrease of CD8+ T cells and loss of tolerance permissive for the formation of ASA.

Seminal plasma possesses immunosuppressive activity. In vitro, large molecules of the seminal plasma were able to suppress the B cell proliferative response induced by the Nocardia mitogen, while small molecules suppressed the T cell proliferative response to phytohemagglutinin A (PHA). Purification of the B cell suppressor factor identified a protein with a molecular weight of 180 kD. This molecule may be able to suppress ASA formation in females, as well as autoantibodies in men [6, 28]. More recent experimental data supporting this hypothesis is still lacking. The immunosuppressive effect, however, is of relevance in the regulation of the immune activity against spermatozoa in the female genital tract (see Chap. 10)

Munoz et al. [17] determined the number of α/β+ and γ/δ+ T cells in serum and semen of 23 men. In a cohort of 7 men with ASA, the mean numbers of γ/δ and α/β T cells were 3,560 and 3,230 cells/ml semen, respectively. In contrast, a group of 16 men with no evidence of autoimmunity to sperm showed a mean number of 350 γ/δ+ T cells and 610 α/β+ T cells/ml semen. The numbers of γ/δ+ and α/β+ T cells in the peripheral blood of the identical men were unrelated to their antisperm antibody status. Thus, γ/δ+ T cells in human semen comprise a larger proportion of the total T cell population than of the T cells in blood. The number of γ/δ+ T cells appeared to be elevated in the semen of men with evidence of localized autoimmunity to their own sperm. These results suggest that the proliferative response of T cells with a γ/δ+ TCR favors an autoimmune response to sperm. The higher proportion of lymphocytes bearing a γ/δ+ antigen receptor in the testis as compared to peripheral blood was also confirmed by Bertotto et al. [5]. The rise of γ/δ+ T cells was mainly due to an overexpansion of cells expressing Vδ1 gene-encoded determinants on their surface. This finding points to a special immune milieu in the semen.

T cells in semen appear to be target cells of HIV infection. Bernard-Stoecklin et al. [4] investigated seminal leukocytes in macaques after infection with SIV and found infection of CD4⁺ T lymphocytes together with macrophages. The lymphocytes had a mucosal phenotype and expressed activation and migration markers. Thus, seminal T cells may facilitate sexual transmission of the immunodeficiency virus.

The presence of T lymphocytes in semen may be of relevance not only regarding their specificity to sperm antigens, but also due to their secretion of cytokines which may influence sperm function. Sperm cells express IFN-α and IFN-γ receptors. IFN-α, IFN-γ, and other cytokines have deleterious effect on sperm motility and fertilizing ability [19]. This may concern also female lymphocytes within the genital tract [9]. Seminal fluid induces an inflammatory reaction in the female genital tract, which results in the secretion of cytokines from the female side that in turn have a range of effects on conception and pregnancy, e.g., the priming of the female immune response to paternal antigens to promote T cell-mediated immune tolerance [25].

In addition, the membrane cofactor protein (MCP), also known as CD46, is a link between T cells and sperm function. CD46 is a multitasking molecule in complement regulation and as a costimulatory molecule for T cell activation. It exists as multiple isomeric forms while human spermatozoa express only an isoform comprising the four short consensus repeat (SCR) domains, the short Ser/Thr/Pro-rich domain C, and the Cyt2 variant of the cytoplasmic tail. Spermatozoal CD46 is identical to the previously described acrosome-restricted spermatozoal protein trophoblast-leukocyte common antigen. Because of its acrosome-restricted expression pattern, spermatozoal CD46 has been utilized as a specific acrosome marker in humans [15, 16]. From further studies it appears that also other CD molecules associated with the immune system may be involved in the fertilization process, such as CD9, CD29, and CD49 [10].