The rodent testis has long been considered a site of immune privilege, where immune responses are suppressed. Evidence for immunosuppression in the primate testis, however, is inconclusive. Indeed, the leukocytes populating the primate testis are mostly uncharacterised. We have used the pigtailed macaque model to characterise macaque testicular leukocytes, their responses to SIV infection, and the strength of immune responses in this region.
Testes from six uninfected and four SIVmac239-infected macaques were studied. Testes were recovered by unilateral orchidectomy 10 weeks after infection. Testis tissue samples were fixed in Bouin’s or formalin, and sections stained with PAS or subjected to immunohistochemistry to detect leukocytes. Interstitial cells were isolated by collagenase digestion of testis tissue and phenotyped using flow cytometry. T-cell responses to mitogen stimulation were measured by intracellular cytokine staining for TNF and IFNγ.
The leukocyte population of the uninfected macaque testes consisted of >45% monocytes and macrophages, 15% CD4+ T-cells, 16% CD8+ T-cells and smaller populations of dendritic, NK and NKT cells. In uninfected animals, T-cell responses to mitogens were highly suppressed in the testis compared to blood, indicating that the primate testis is immune-privileged. SIV infection of the testis did not lead to major disruptions to spermatogenesis or testicular architecture. Infection did, however, decrease the proportion of testicular CD4+ “helper” T-cells, the targets of infection, and increase CD8+ “cytotoxic” T-cells, which likely enter the testis in response to infection. Macrophages were decreased whereas granulocytes numbers increased.
Our data provide the first detailed characterisation of primate testicular leukocytes and evidence in favour of immunosuppression in the primate testis. SIV infection of the testis led to severe depletion of target CD4+ T-cells and an influx of cytotoxic cells. Whether these cells can respond to infection in this immunosuppressive environment requires further investigation.