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Cytotoxic CD4+CD28 null T lymphocytes, systemic inflammation and atherosclerotic risk in patients with chronic kidney

Ashok Kumar Yadav1, Anupam Lal, Vivekanand Jha

  • 1Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Nephron. Clinical Practice
|August 22, 2012
PubMed

Insights

Chronic kidney disease (CKD) patients show increased CD4(+)CD28(null) T cells, which are cytotoxic and linked to early atherosclerosis. Tumor necrosis factor-alpha (TNF-α) may drive this expansion in CKD.

Area of Science:

  • Immunology
  • Nephrology
  • Cardiovascular Disease

Background:

  • CD4(+) T cells lacking CD28 (CD4(+)CD28(null)) are implicated in atherosclerosis.
  • The role of CD4(+)CD28(null) T cells in early atherosclerotic changes in chronic kidney disease (CKD) remains uninvestigated.

Purpose of the Study:

  • To evaluate the frequency of circulating CD4(+)CD28(null) T cells in CKD patients.
  • To assess the association between CD4(+)CD28(null) T cells and preclinical atherosclerotic changes in CKD.

Main Methods:

  • Flow cytometry was used to determine CD4(+)CD28(null) cell phenotype and cytotoxic potential (perforin, granzyme B).
  • Systemic inflammation markers (hsCRP, IL-6, TNF-α) were measured by ELISA.
  • Carotid intima-media thickness (CCA-IMT) was assessed via ultrasound; in vitro experiments explored cytokine effects.

Main Results:

  • CKD patients exhibited significantly higher frequencies of CD4(+)CD28(null) cells compared to controls.
  • These cells showed increased cytotoxic markers and correlated positively with CCA-IMT.
  • Elevated TNF-α levels in CKD correlated with CD4(+)CD28(null) cells, and TNF-α induced CD28 downregulation in vitro.

Conclusions:

  • CKD is associated with an expanded population of circulating cytotoxic CD4(+)CD28(null) T lymphocytes.
  • The expansion of CD4(+)CD28(null) cells correlates with preclinical atherosclerotic changes in CKD.
  • TNF-α appears to play a specific role in the expansion of this T cell subset in CKD patients.
Abstract

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