Characterization of myeloid cell populations in human testes collected after sex reassignment surgery

J Reprod Immunol. 2018 Feb:125:16-24. doi: 10.1016/j.jri.2017.10.043. Epub 2017 Oct 14.

Abstract

The testis has been described in animal models as a site of immune privilege, which protects spermatids against tissue damage during inflammation. Myeloid cells, including macrophages and dendritic cells (DC), are defined as key players in the testicular immune privilege in animal models. However, their distribution and frequency in human testis remain poorly described. To overcome the challenges related to tissue sampling, we obtained testicular tissue from men under hormonal therapy who elected to have sex reassignment surgery (SRS). We examined the distribution of myeloid cell populations in tissue sections using immunohistofluorescence and evaluated their relative frequencies in fresh testicular cell suspensions compared with matched blood using multi-parametric flow cytometry. We identified 4.9% of CD45+ leucocytes in testicular cell suspensions, of which 0.4% were B cells, demonstrating a low level of blood contamination. Myeloid cells (Lin-HLA-DR+) were located in the testicular interstitium and represented a median of 23.4% of testicular leucocytes, displaying higher HLA-DR expression compared to their counterparts in blood (p=0.001). The frequency of testicular myeloid cells was not linked with the duration of hormonal therapy. Resident macrophages (CD14+CD163+) constituted the most frequent myeloid cell subset and expressed high levels of CD163. Elevated proportion of myeloid DC (CD14-CD11c+) contrasted with the paucity of plasmacytoïd DC (CD14-CD123+) in testis. Myeloid-derived suppressor cells (Lin-HLA-DR-CD33hiCD11bhi) were not detected in the testis while constituting 0.5% of blood leucocytes. For the first time, we characterized myeloid cell subsets in human testes collected after SRS, providing a basis to assess their contribution to immune privilege.

Keywords: Human testis; Immune privilege; MDSC; Resident macrophages; mDC; pDC.

MeSH terms

  • Adult
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • CD11b Antigen / immunology
  • CD11b Antigen / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Estradiol / administration & dosage
  • Hormone Replacement Therapy / methods*
  • Humans
  • Interleukin-3 Receptor alpha Subunit / immunology
  • Interleukin-3 Receptor alpha Subunit / metabolism
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharide Receptors / metabolism
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Myeloid-Derived Suppressor Cells / drug effects
  • Myeloid-Derived Suppressor Cells / immunology*
  • Myeloid-Derived Suppressor Cells / metabolism
  • Orchiectomy
  • Progesterone / administration & dosage
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism
  • Sex Reassignment Surgery
  • Sialic Acid Binding Ig-like Lectin 3 / immunology
  • Sialic Acid Binding Ig-like Lectin 3 / metabolism
  • Spironolactone / administration & dosage
  • Testis / cytology*
  • Testis / drug effects
  • Testis / immunology
  • Testis / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD11b Antigen
  • CD14 protein, human
  • CD163 antigen
  • CD33 protein, human
  • IL3RA protein, human
  • ITGAM protein, human
  • Interleukin-3 Receptor alpha Subunit
  • Lipopolysaccharide Receptors
  • Receptors, Cell Surface
  • Sialic Acid Binding Ig-like Lectin 3
  • Spironolactone
  • Progesterone
  • Estradiol