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Regulatory IgDhi B Cells Suppress T Cell Function via IL-10 and PD-L1 during Progressive Visceral Leishmaniasis
Journal article   Peer reviewed

Regulatory IgDhi B Cells Suppress T Cell Function via IL-10 and PD-L1 during Progressive Visceral Leishmaniasis

Robert G Schaut, Ian M Lamb, Angela J Toepp, Benjamin Scott, Carolina O Mendes-Aguiar, Jose F V Coutinho, Selma M B Jeronimo, Mary E Wilson, John T Harty, Thomas J Waldschmidt, …
The Journal of immunology (1950), Vol.196(10), pp.4100-4109
05/15/2016
DOI: 10.4049/jimmunol.1502678
PMCID: PMC4868652
PMID: 27076677

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Abstract

During visceral leishmaniasis (VL), Th1-based inflammation is induced to control intracellular parasites. Inflammation-based pathology was shown to be dampened by IL-10 and eventual programmed death 1-mediated T cell exhaustion. Cell type(s) responsible for the initiation of T cell-produced IL-10 during VL are unknown. CD19(+), CD5(-), CD1d(-), IgD(hi) regulatory B cells from healthy controls produced IL-10 in the absence of infection or stimulation, in contrast to IgD(lo/neg) B cells. IgD(hi) B cells may have a de novo versus induced regulatory program. The population of IgD(hi) B cells increased 3-fold as VL progressed. B cells from VL dogs were necessary and sufficient to suppress Th1 cell effector function. IgD(hi) B cells induced IL-10 production by T cells and IgD(lo) B cells. Blockage of B cell-specific PD-L1 restored Th1 responses. IgD(hi) regulatory B cells represent a novel regulatory B cell that may precipitate T cell exhaustion during VL.
Antibodies, Blocking - metabolism Antigens, Protozoan - immunology Immunoglobulin D - metabolism Humans Cells, Cultured Immune Tolerance Male Leishmaniasis, Visceral - immunology B-Lymphocytes, Regulatory - immunology Th1 Cells - immunology B7-H1 Antigen - immunology Disease Progression B-Lymphocytes, Regulatory - parasitology B7-H1 Antigen - metabolism Animals Dogs Interleukin-10 - metabolism Leishmania infantum - immunology Th1 Cells - parasitology Female Protozoan Proteins - immunology Antibodies, Protozoan - metabolism

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