Interaction between human mature adipocytes and lymphocytes induces T-cell proliferation

Cytotherapy. 2015 Sep;17(9):1292-301. doi: 10.1016/j.jcyt.2015.06.007.

Abstract

Background aims: Adipose tissue is a critical organ that plays a major role in energy balance regulation and the immune response through intricate signals.

Methods: We report on the inter-relation between mature adipocytes and lymphocytes in terms of adipocyte-derived T-cell chemo-attractants and adipocyte metabolic effects on lymphocytes.

Results: During the culture time, mature adipocytes changed their structural and functional properties into de-differentiated cells. Isolated mature adipocytes expressed significantly higher levels of CIITA, major histocompatibility complex II (human leukocyte antigen [HLA]-DR) and costimulatory signal molecule CD80 compared with adipocytes after the de-differentiation process. Moreover, human leukocyte antigen-G, which may prevent the immune responses of mesenchymal stromal cells, was expressed at lower level in mature adipocytes compared with de-differentiated adipocytes. In line with these molecular data, functional results showed different immunoregulatory properties between adipocytes before and after the de-differentiation process. Mature adipocytes stimulated the proliferation of total lymphocytes and immunoselected cell populations CD3+, CD4+ and CD8+ in a direct contact-dependent way that involved the major histocompatibility complex I and II pathways. Moreover, adipocytes secreted potential chemo-attractant factors, but data showed that adipocyte-derived culture medium was not sufficient to activate lymphocyte proliferation, suggesting that a direct contact between adipocytes and immune cells was needed. However, specific mature adipocyte cytokines enhanced lymphocyte proliferation in a mixed lymphocyte reaction.

Conclusions: In conclusion, cross-talk occurs between adipocytes and lymphocytes within adipose tissue involving T-cell chemo-attraction by mature adipocytes. Our findings, together with current observations in the field, provide a rationale to identify adipocyte-lymphocyte cross-talk that instigates adipose inflammation.

Keywords: T-cell activation; de-differentiated adipocytes; inflammation; mature adipocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / immunology*
  • Adipose Tissue / cytology
  • Adipose Tissue / immunology*
  • Adipose Tissue / physiology
  • Aged
  • Aged, 80 and over
  • B7-1 Antigen / immunology
  • Cell Communication / immunology*
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • HLA-DR Antigens / immunology
  • HLA-G Antigens / biosynthesis
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Inflammation / immunology*
  • Lymphocyte Activation / immunology
  • Lymphocyte Culture Test, Mixed
  • Mesenchymal Stem Cells / immunology
  • Middle Aged
  • Nuclear Proteins / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Trans-Activators / immunology

Substances

  • B7-1 Antigen
  • Cytokines
  • HLA-DR Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • MHC class II transactivator protein
  • Nuclear Proteins
  • Trans-Activators