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Single-cell Analysis of Immunophenotype and Cytokine Production in Peripheral Whole Blood via Mass Cytometry
Published on: June 26, 2018
Imbalance of CD4+ lymphocyte subsets in patients with mixed connective tissue disease
H Becker1, A Langrock, K Federlin
1III. Medizinische Klinik und Poliklinik, Universität Giessen, Germany.
Insights
Patients with mixed connective tissue disease (MCTD) show altered CD4+ T lymphocyte subsets. Specifically, CD4+CD45RA+ cells increase while CD4+CD29+ cells decrease, suggesting potential immune dysregulation in MCTD.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Mixed connective tissue disease (MCTD) is an autoimmune disorder with features of other connective tissue diseases.
- CD4+ T lymphocytes play a crucial role in immune regulation.
- Alterations in T lymphocyte subsets may contribute to the pathogenesis of autoimmune diseases.
Purpose of the Study:
- To investigate the proportions of specific CD4+ T lymphocyte subsets in patients with MCTD.
- To compare these subsets with those in healthy controls and patients with progressive systemic sclerosis.
- To explore the activation and phenotype acquisition of CD4+ T cells in MCTD.
Main Methods:
- Double-labeling immunofluorescence was used to analyze peripheral blood samples.
- Flow cytometry was employed to quantify CD4+CD45RA+ and CD4+CD29+ T cells.
- Phytohaemagglutinin stimulation was used to assess T cell activation and phenotype changes.
Main Results:
- Patients with MCTD exhibited a significantly higher proportion of CD4+CD45RA+ cells compared to controls (P<0.01).
- A marked decrease in CD4+CD29+ cells was observed in MCTD patients (P<0.001).
- CD4+CD29+ cells were lower in MCTD than in patients with progressive systemic sclerosis; MCTD CD4+ cells showed enhanced CD29+ phenotype acquisition upon stimulation.
Conclusions:
- MCTD is characterized by an imbalance in CD4+ T lymphocyte subsets, with increased naive (CD45RA+) and decreased memory/effector (CD29+) cells.
- The enhanced in vivo responsiveness and potential tissue accumulation of CD4+CD29+ cells may lead to their depletion in peripheral blood.
- These findings suggest a role for altered CD4+ T cell dynamics in the pathogenesis of MCTD.
Abstract:
CD4+ (helper/inducer) T lymphocyte subsets were studied in the peripheral blood from patients with mixed connective tissue disease (MCTD) by double-labelling immunofluorescence. The proportion of CD4+CD45RA+ cells was higher (P less than 0.01) when compared with controls, whereas CD4+CD29+ cells were markedly diminished (P less than 0.001). CD4+CD29+ cells were lower than in patients with progressive systemic sclerosis who were studied in parallel. Upon stimulation with phytohaemagglutinin, CD4+ cells from MCTD patients showed a strong reactivity to acquire the CD29+ phenotype. Expression of high levels of CD29 and other adhesion molecules might lead to facilitated localization of CD4+ cells to inflamed tissue. It is suggested that an increased responsiveness of CD4+ cells to activation signals in vivo and accumulation of CD4+CD29+ cells at tissue sites could result in depletion of this cell subset in the peripheral blood of patients with MCTD.
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