CD4 T cell activation by B cells in human Leishmania (Viannia) infection

BMC Infect Dis. 2014 Feb 25;14:108. doi: 10.1186/1471-2334-14-108.

Abstract

Background: An effective adaptive immune response requires activation of specific CD4 T cells. The capacity of B cells to activate CD4 T cells in human cutaneous leishmaniasis caused by Leishmania (Viannia) has not been evaluated.

Methods: CD4 T cell activation by B cells of cutaneous leishmaniasis patients was evaluated by culture of PBMCs or purified B cells and CD4 T cells with Leishmania panamensis antigens. CD4 T cell and B cell activation markers were evaluated by flow cytometry and 13 cytokines were measured in supernatants with a bead-based capture assay. The effect of Leishmania antigens on BCR-mediated endocytosis of ovalbumin was evaluated in the Ramos human B cell line by targeting the antigen with anti-IgM-biotin and anti-biotin-ovalbumin-FITC.

Results: Culture of PBMCs from cutaneous leishmaniasis patients with Leishmania antigens resulted in upregulation of the activation markers CD25 and CD69 as well as increased frequency of CD25hiCD127- cells among CD4 T cells. Concomitantly, B cells upregulated the costimulatory molecule CD86. These changes were not observed in PBMCs from healthy subjects, indicating participation of Leishmania-specific lymphocytes expanded in vivo. Purified B cells from these patients, when interacting with purified CD4 T cells and Leishmania antigens, were capable of inducing significant increases in CD25 and CD69 expression and CD25hiCD127- frequency in CD4 T cells. These changes were associated with upregulation of CD86 in B cells. Comparison of changes in CD4 T cell activation parameters between PBMC and B cell/CD4 T cell cultures showed no statistically significant differences; further, significant secretion of IFN-γ, TNF-α, IL-6 and IL-13 was induced in both types of cultures. Additionally, culture with Leishmania antigens enhanced BCR-mediated endocytosis of ovalbumin in Ramos human B cells.

Conclusions: The capacity of B cells specific for Leishmania antigens in peripheral blood of cutaneous leishmaniasis patients to activate CD4 T cells and induce cytokine secretion is similar to that of all cell populations present in PBMCs. This capacity implicates B cells as a plausible target for modulation of the immune response to Leishmania infection as a therapeutic strategy.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / immunology*
  • Biotin / chemistry
  • CD4-Positive T-Lymphocytes / immunology*
  • Colombia / epidemiology
  • Female
  • Flow Cytometry
  • Fluorescein-5-isothiocyanate / chemistry
  • Gene Expression Regulation
  • Humans
  • Immunoglobulin M / chemistry
  • Interferon-gamma / immunology
  • Interleukin-6 / immunology
  • Leishmania braziliensis / immunology*
  • Leishmaniasis, Cutaneous / blood*
  • Leishmaniasis, Cutaneous / immunology*
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Ovalbumin / chemistry
  • Tumor Necrosis Factor-alpha / immunology
  • Young Adult

Substances

  • Immunoglobulin M
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Biotin
  • Interferon-gamma
  • Ovalbumin
  • Fluorescein-5-isothiocyanate