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AB0019 Hdl promotes a regulatory phenotype of the immune system by inducing the proliferation of human cd4+ t cells while increasing the expression of foxp3 in regulator t cells
  1. M Fernandes Das Neves1,2,
  2. JR Batuca2,
  3. EC Jury3,
  4. J Delgado Alves1,2
  1. 1Medicine IV, Professor Doutor Fernando Fonseca Hospital, Amadora
  2. 2CEDOC - Chronic Disease Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
  3. 3Centre for Rheumatology Research, University College London, London, United Kingdom

Abstract

Background High-density lipoproteins (HDL) are the plasma lipoproteins responsible for reverse cholesterol transport. Its protective effect on cardiovascular disease is attributed to the cholesterol efflux capacity as well as to its anti-oxidant and anti-inflammatory properties. HDL low levels are associated with immune diseases, including systemic lupus erythematosus and rheumatoid arthritis, implying a potential link between HDL and immunity.

There is few evidence on the effects of HDL on human T cells. Animal studies suggested that HDL inhibits lymphocyte proliferation1, but the only study in humans showed that HDL from young and healthy subjects increases the proliferation of lymphocytes2. Previous studies also showed that HDL levels are positively correlated with the prevalence of regulator T cells in peripheral blood3.

Furthermore, it has been shown that one of the main actions of HDL in lymphocytes is the disaggregation of lipid rafts provoked by cholesterol efflux from the membrane, but the final consequences of this effect are not known.

Objectives To determine the in vitro effects of HDL in human T cell proliferation and in the frequency of FoxP3+ regulator T cells.

Methods Peripheral blood mononuclear cells from six healthy donors were cultured with and without HDL to measure membrane cholesterol and proliferative response to CD3/CD28 stimulation. Membrane cholesterol was measured by filipin binding, assessed by flow cytometry. T cell proliferation was studied by Ki-67 expression and cell trace staining for multiple generations. T cell phenotyping and FoxP3 fluorescence were analyzed by flow cytometry.

Results HDL significantly reduced the amount of membrane cholesterol in CD4+ T cells, after 24 hours in culture. When added in the absence of stimulation, HDL did not induce any proliferation in CD4+ T cells. When added in conjunction with CD3/CD28 stimulation, HDL significantly increased the proliferation of CD4+ T cells. T cell phenotyping showed a significant increase in CD4+CD25+ FoxP3 fluorescence, after culture with HDL.

Conclusions This study shows that HDL promotes cholesterol efflux from the membrane of CD4+ T cells in vitro and increases CD4+ T cell proliferation. However, the increase in T cell numbers seem to favor the expression of FoxP3 in regulator in T cells, which is associated with suppression of inflammation. With the development of therapies to increase HDL levels, the knowledge of the HDL effects on T cell subsets is very important for the future management of cardiovascular and rheumatic diseases.

References

  1. Wilhem AJ, Zabalawi M, Owen JS, et al. Apolipoprotein A-I modulates regulatory T cells in autoimmune LDLr-/-, ApoA-I-/- mice. J Biol Chem. 2010; 285:36158–36169.

  2. Larbi A, Fortin C, Dupuis G, et al. Immunomodulatory role of high-density lipoproteins: impact on immunosenescence. Age. 2014; 36(5):9712.

  3. Ammirati E, Cianflone D, Banfi M, et al. Circulating CD4+CD25hiCD127lo regulatory T-cell levels do not reflect the extent or severity of carotid and coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 2010; 30:1832–1841.

References

Disclosure of Interest None declared

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