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AB0011 KLRG1 as a marker of CD28 negativity in rheumatoid arthritis, comparison with CD57 and CD45RA
  1. C Rawlings,
  2. E Choy,
  3. R Davies,
  4. G Jones,
  5. A Williams
  1. Cardiff University, Cardiff, United Kingdom

Abstract

Background Our research has shown that patients with RA have higher proportions of peripheral blood CD3+CD8+CD28- Treg cells compared to healthy individuals. CD3+CD8+CD28- Treg cells in patients with RA have lost their ability to suppress lymphocyte proliferation1. Thus CD28 negativity may mark senescent T cells. CD572 CD45RA3,4 and killer-cell lectin like receptor G1 (KLRG1)5 cell surface molecules have been associated with CD8+ T cell activation and senescence. Defining the phenotypic signature of CD8+CD28- Treg cells will help establish their significance in the immunoregulation of RA.

Objectives To use immunofluorescence and flow cytometry to define the phenotype of CD3+CD8+CD28+/- cells in relation to early RA progression.

Methods The effector characteristics of peripheral blood CD8 T cells were evaluated by flow cytometry. RA patients with established (n=21) and early disease (n=20) were recruited, and compared to twenty four healthy controls. The mean age of the subjects was 59 (SD=12.5), 25/38 (66%) were female, 27/38 (71%) were anti-CCP positive and 25/38 (66%) rheumatoid factor positive. The mean age for the controls was 43 (SD=11.6), 14/20 (70%) were female.

Results Confirming our previous work, a significantly higher proportion of CD3+CD8+CD28- cells was observed in RA patients compared to healthy individuals (P=0.03) (Figure 1).

Flow cytometric evaluation of peripheral blood demonstrated a significantly higher expression of CD57, CD45Ra and KLRG1 in CD28- compared to CD28+ T cells.

Table 1.

CD57, CD45Ra, KLRG1 and CD28 on CD3+CD8+ T cells

A further evaluation of these markers revealed that 69% of the CD8+CD28- cell pool was KLRG1+, in comparison to 66% being CD57+ and 55% KLRG1+CD57+ double positive. This suggests that KLRG1 is a robust and clinically relevant marker of CD28- T cells in RA. Our current research is investigating the significance of KLRG1 and CD8+CD28- cells as prognostic markers in RA.

Conclusions CD3+CD8+CD28- cells are enriched in the peripheral blood of RA patients. KLRG1 expression is increased in line with CD57 and CD45Ra in CD8+CD28- cells, and will be used to evaluate the functional significance of these cells in relation to their activation status and potential senescence in the immunoregulation of RA pathogenesis.

References

  1. Ceeraz S, Hall C, Choy EH, Spencer J, Corrigall VM. Defective CD8+CD28+ regulatory T cell suppressor function in rheumatoid arthritis is restored by tumour necrosis factor inhibitor therapy. Clin Exp Immunol. 2013 Oct;174(1):18–26.

  2. Progressive decrease of CD8high+ CD28+ CD57- cells with ageing.Merino J, Martínez-González MA, Rubio M, Inogés S, Sánchez-Ibarrola A, Subirá ML Clin Exp Immunol. 1998 Apr; 112(1):48–51.

  3. CD28(-)CD8(+) T cells do not contain unique clonotypes and are therefore dispensable. Weinberger B, Welzl K, Herndler-Brandstetter D, Parson W, Grubeck-Loebenstein BImmunol Lett. 2009 Dec 2; 127(1):27–32.

  4. KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells. Henson SM, Franzese O, Macaulay R, Libri V, Azevedo RI, Kiani-Alikhan S, Plunkett FJ, Masters JE, Jackson S, Griffiths SJ, Pircher HP, Soares MV, Akbar AN. Blood. 2009 Jun 25; 113(26):6619–28.

References

Disclosure of Interest None declared

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