Subpopulations of M-MDSCs from mice infected by an immunodeficiency-causing retrovirus and their differential suppression of T- vs B-cell responses

Virology. 2015 Nov:485:263-73. doi: 10.1016/j.virol.2015.07.020. Epub 2015 Aug 27.

Abstract

Monocytic (CD11b(+)Ly6G(±/Lo)Ly6C(+)) myeloid derived suppressor cells (M-MDSCs) expand following murine retroviral LP-BM5 infection and suppress ex vivo polyclonal T-cell and B-cell responses. M-MDSCs 3 weeks post LP-BM5 infection have decreased suppression of T-cell, but not B-cell, responses and alterations in the degree of iNOS/NO dependence of suppression. M-MDSCs from LP-BM5 infected mice were sorted into four quadrant populations (Ly6C/CD11b density): all quadrants suppressed B-cell responses, but only M-MDSCs expressing the highest levels of Ly6C and CD11b (Q2) significantly suppressed T-cell responses. Further subdivision of this Q2 population revealed the Ly6C(+/Hi) M-MDSC subpopulation as the most suppressive, inhibiting T- and B-cell responses in a full, or partially, iNOS/NO-dependent manner, respectively. In contrast, the lower/moderate levels of suppression by the Ly6C(+/Lo) and Ly6C(+/Mid) M-MDSC Q2 subpopulations, whether versus T- and/or B-cells, displayed little/no iNOS dependency for suppression. These results highlight differential phenotypic and functional immunosuppressive M-MDSC subsets in a retroviral immunodeficiency model.

Keywords: LP-BM5; Myeloid derived suppressor cells; Retrovirus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism
  • Antigens, Ly / genetics
  • Antigens, Ly / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD11b Antigen / genetics
  • CD11b Antigen / metabolism
  • Gene Expression
  • Immunomodulation
  • Immunophenotyping
  • Mice
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism
  • Myeloid Cells / virology*
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism
  • Retroviridae / immunology*
  • Retroviridae Infections / genetics
  • Retroviridae Infections / immunology
  • Retroviridae Infections / metabolism
  • Retroviridae Infections / virology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antigens, Differentiation
  • Antigens, Ly
  • CD11b Antigen
  • Ly-6C antigen, mouse
  • Receptors, Chemokine
  • monocyte-macrophage differentiation antigen