CD4+,CD28- T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems

Arthritis Rheum. 2001 Jan;44(1):13-20. doi: 10.1002/1529-0131(200101)44:1<13::AID-ANR3>3.0.CO;2-6.

Abstract

Objective: To determine whether CD4+,CD28- T cells, which are expanded in patients with rheumatoid arthritis (RA), express receptors that typically regulate the function of natural killer (NK) cells.

Methods: Expression of the NK cell surface molecules CD158, p70, CD94, CD161, and CD8alpha on T cell subsets was determined by multicolor flow cytometric analysis of peripheral blood mononuclear cells from 36 RA patients. Expression of CD161 on tissue-infiltrating CD4 T cells was determined by 2-color immunohistochemistry analysis of synovial tissue samples.

Results: Killer cell-inhibitory receptors (KIR) and killer cell-activating receptors (KAR) were exclusively expressed on CD4+,CD28- T cells, with the CD158b molecule being the most frequently detected isoform. A coordinated mechanism inducing KIR/KAR expression was suggested by similarities in the expression of CD158b on CD4 and CD8 T cells. CD4+,CD28- T cells were also positive for CD8-alphaalpha homodimers, another characteristic shared with NK cells. Of the C-type lectin NK cell receptors (NK receptors), CD94 was consistently absent, but CD161 was found on a CD4 T cell population that is significantly expanded in RA patients (P = 0.01). Involvement in disease of NK receptor-expressing CD4 T cells was suggested by the presence of CD4+,CD161+ T cells in follicular microstructures typical of rheumatoid synovitis.

Conclusion: Patients with RA have an expanded and unusual subset of CD4 T cells that infiltrates the tissue lesions and is characterized by a deficiency of CD28, the expression of CD8-alphaalpha homodimers, and the expression of several types of HLA class I-recognizing NK receptors. CD4 T cells bearing NK receptors can bridge functions of the innate and adaptive immune systems, such as responsiveness to specific antigen, rapid release of interferon-gamma, cytotoxicity, independence from classic costimulatory pathways, and integration of multiple activating and inhibitory signals to control effector functions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Surface / analysis
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / pathology*
  • CD28 Antigens / analysis*
  • CD4-Positive T-Lymphocytes / immunology*
  • Immune System / physiology
  • Immunity, Innate
  • Killer Cells, Natural / immunology
  • Lectins, C-Type*
  • NK Cell Lectin-Like Receptor Subfamily B
  • Receptors, Immunologic / analysis
  • Synovial Membrane / immunology
  • T-Lymphocytes / immunology*

Substances

  • Antigens, Surface
  • CD28 Antigens
  • Lectins, C-Type
  • NK Cell Lectin-Like Receptor Subfamily B
  • Receptors, Immunologic