Complement receptor type 1 (CR1/CD35) expressed on activated human CD4+ T cells contributes to generation of regulatory T cells

Katalin Török, B. Dezső, András Bencsik, Barbara Uzonyi, A. Erdei

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The role of complement in the regulation of T cell immunity has been highlighted recently by several groups. We were prompted to reinvestigate the role of complement receptor type 1 (CR1, CD3) in human T cells based on our earlier data showing that activated human T cells produce C3 (Torok et al. (2012) [48]) and also by results demonstrating that engagement of Membrane Cofactor Protein (MCP, CD46) induces a switch of anti-CD3-activated helper T cells into regulatory T cells (Kemper et al. (2003) [17]). We demonstrate here that co-ligation of CD46 and CD3, the two C3b-binding structures present on activated CD4+ human T cells significantly enhances CD25 expression, elevates granzyme B production and synergistically augments cell proliferation. The role of CR1 in the development of the Treg phenotype was further confirmed by demonstrating that its engagement enhances IL-10 production and reduces IFNγ release by the activated CD4+ T cells in the presence of excess IL-2. The functional in vivo relevance of our findings was highlighted by the immunohistochemical staining of tonsils, revealing the presence of CD4/CD3 double positive lymphocytes mainly in the inter-follicular regions where direct contact between CD4+ T cells and B lymphocytes occurs.Regarding the in vivo relevance of the complement-dependent generation of regulatory T cells in secondary lymphoid organs we propose a scenario shown in the figure. The depicted process involves the sequential binding of locally produced C3 fragments to CD46 and CD3 expressed on activated T cells, which - in the presence of excess IL-2 - leads to the development of Treg cells.

Original languageEnglish
Pages (from-to)117-124
Number of pages8
JournalImmunology Letters
Volume164
Issue number2
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Complement Receptors
Regulatory T-Lymphocytes
T-Lymphocytes
Interleukin-2
CD46 Antigens
Granzymes
Palatine Tonsil
Helper-Inducer T-Lymphocytes
Interleukin-10
Ligation
Immunity
B-Lymphocytes
Cell Proliferation
Lymphocytes
Staining and Labeling
Phenotype

Keywords

  • CD4+ human T cells
  • CR1 (CD35) expression
  • Synergism with MCP (CD46)
  • Treg differentiation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Complement receptor type 1 (CR1/CD35) expressed on activated human CD4+ T cells contributes to generation of regulatory T cells. / Török, Katalin; Dezső, B.; Bencsik, András; Uzonyi, Barbara; Erdei, A.

In: Immunology Letters, Vol. 164, No. 2, 01.04.2015, p. 117-124.

Research output: Contribution to journalArticle

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