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CD45RC isoform expression identifies functionally distinct T cell subsets differentially distributed between healthy individuals and AAV patients.

Ordonez L, Bernard I, L'faqihi-Olive FE, Tervaert JW, Damoiseaux J, Saoudi A - PLoS ONE (2009)

Bottom Line: Interestingly, AAV patients exhibit an increased proportion of CD45RC(low) CD4 T cells as compared to HC and SLE patients.In conclusion, we have shown that CD45RC expression divides human T cells in functionally distinct subsets that are imbalanced in AAV.Since this imbalance is stable over time and independent of several disease parameters, we hypothesize that this is a pre-existing immune abnormality involved in the etiology of AAV.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U563, Institut Fédératif de Recherche (IFR) 30, Hôpital Purpan and Université Paul Sabatier, Toulouse, France.

ABSTRACT
In animal models of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), the proportion of CD45RC T cell subsets is important for disease susceptibility. Their human counterparts are, however, functionally ill defined. In this report, we studied their distribution in healthy controls (HC), AAV patients and in Systemic lupus erythematous (SLE) patients as disease controls. We showed that CD45RC expression level on human CD4 and CD8 T cells identifies subsets that are highly variable among individuals. Interestingly, AAV patients exhibit an increased proportion of CD45RC(low) CD4 T cells as compared to HC and SLE patients. This increase is stable over time and independent of AAV subtype, ANCA specificity, disease duration, or number of relapses. We also analyzed the cytokine profile of purified CD4 and CD8 CD45RC T cell subsets from HC, after stimulation with anti-CD3 and anti-CD28 mAbs. The CD45RC subsets exhibit different cytokine profiles. Type-1 cytokines (IL-2, IFN-gamma and TNF-alpha) were produced by all CD45RC T cell subsets, while the production of IL-17, type-2 (IL-4, IL-5) and regulatory (IL-10) cytokines was restricted to the CD45RC(low) subset. In conclusion, we have shown that CD45RC expression divides human T cells in functionally distinct subsets that are imbalanced in AAV. Since this imbalance is stable over time and independent of several disease parameters, we hypothesize that this is a pre-existing immune abnormality involved in the etiology of AAV.

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CD45RC T cell subsets distribution in healthy individuals and ANCA patients.Peripheral blood leukocytes from 39 healthy individuals (HC), 38 patients with ANCA-associated vasculitis (AAV), and 20 patients with systemic lupus erythematosus (SLE), were stained with mAbs against CD3, CD4, CD8, CD45RC. (A) The proportion of CD45RClow CD4 T cells (left panel) and the proportion of CD45RChigh-CD45RCint-CD45RClow CD8 T cells (right three panels) are presented as box plot diagrams for each study population. The p-values were calculated using the Wilcoxon matched-pairs test; p<0.05; **, p<0.02; ***, p<0.002. (B) The proportion of CD45RClow CD4 T cells are presented according to disease subtype (WG, Wegener's granulomatosis; MPA, microscopic polyangiitis; CSS, Churg-Strauss Syndrome; RLV, renal limited vasculitis), type of ANCA specificity (MPO, myeloperoxidase; PR3, proteinase 3), renal involvement (no: no kidney disease; yes: kidney disease), and relapses (no: no relapse; yes: relapses). Data are presented as box plot diagrams for each study population. The p-values were calculated using Mann Witney U test; *p<0.05. The proportion of CD45RClow CD4 T cells are presented according to duration of disease (C, left panel). The proportion of CD45RClow CD4 T cells of 18 AAV patients (13 WG, 3 MPA, and 2 RLV patients) at 4 years interval (C, right panel).
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pone-0005287-g003: CD45RC T cell subsets distribution in healthy individuals and ANCA patients.Peripheral blood leukocytes from 39 healthy individuals (HC), 38 patients with ANCA-associated vasculitis (AAV), and 20 patients with systemic lupus erythematosus (SLE), were stained with mAbs against CD3, CD4, CD8, CD45RC. (A) The proportion of CD45RClow CD4 T cells (left panel) and the proportion of CD45RChigh-CD45RCint-CD45RClow CD8 T cells (right three panels) are presented as box plot diagrams for each study population. The p-values were calculated using the Wilcoxon matched-pairs test; p<0.05; **, p<0.02; ***, p<0.002. (B) The proportion of CD45RClow CD4 T cells are presented according to disease subtype (WG, Wegener's granulomatosis; MPA, microscopic polyangiitis; CSS, Churg-Strauss Syndrome; RLV, renal limited vasculitis), type of ANCA specificity (MPO, myeloperoxidase; PR3, proteinase 3), renal involvement (no: no kidney disease; yes: kidney disease), and relapses (no: no relapse; yes: relapses). Data are presented as box plot diagrams for each study population. The p-values were calculated using Mann Witney U test; *p<0.05. The proportion of CD45RClow CD4 T cells are presented according to duration of disease (C, left panel). The proportion of CD45RClow CD4 T cells of 18 AAV patients (13 WG, 3 MPA, and 2 RLV patients) at 4 years interval (C, right panel).

Mentions: The analysis of CD45RC T cell subsets in the peripheral blood of patients with AAV, all in clinical remission, revealed a strong predominance of the CD45RClow subset within the CD4, but not the CD8 T cell compartment (Fig. 3A). Interestingly, we did not observe this increased proportion of CD45RClow CD4 T cells in patients with SLE, another chronic systemic autoimmune disease (Fig. 3A). The percentage of CD45RC CD4 T cells was not different between patients with the distinct disease entities of AAV (WG, MPA, CSS, and renal limited vasculitis), MPO− or PR3-ANCA, or number of relapses (Fig. 3B). Interestingly, the proportion of CD4 CD45RClow subset was significantly higher in AAV patients with renal involvement (Fig. 3B, right panel). Finally, the observed increased proportion of the CD45RClow CD4 T cells in AAV patients was not influenced by the duration of the disease and was stable during 4 year follow-up (Fig. 3C).


CD45RC isoform expression identifies functionally distinct T cell subsets differentially distributed between healthy individuals and AAV patients.

Ordonez L, Bernard I, L'faqihi-Olive FE, Tervaert JW, Damoiseaux J, Saoudi A - PLoS ONE (2009)

CD45RC T cell subsets distribution in healthy individuals and ANCA patients.Peripheral blood leukocytes from 39 healthy individuals (HC), 38 patients with ANCA-associated vasculitis (AAV), and 20 patients with systemic lupus erythematosus (SLE), were stained with mAbs against CD3, CD4, CD8, CD45RC. (A) The proportion of CD45RClow CD4 T cells (left panel) and the proportion of CD45RChigh-CD45RCint-CD45RClow CD8 T cells (right three panels) are presented as box plot diagrams for each study population. The p-values were calculated using the Wilcoxon matched-pairs test; p<0.05; **, p<0.02; ***, p<0.002. (B) The proportion of CD45RClow CD4 T cells are presented according to disease subtype (WG, Wegener's granulomatosis; MPA, microscopic polyangiitis; CSS, Churg-Strauss Syndrome; RLV, renal limited vasculitis), type of ANCA specificity (MPO, myeloperoxidase; PR3, proteinase 3), renal involvement (no: no kidney disease; yes: kidney disease), and relapses (no: no relapse; yes: relapses). Data are presented as box plot diagrams for each study population. The p-values were calculated using Mann Witney U test; *p<0.05. The proportion of CD45RClow CD4 T cells are presented according to duration of disease (C, left panel). The proportion of CD45RClow CD4 T cells of 18 AAV patients (13 WG, 3 MPA, and 2 RLV patients) at 4 years interval (C, right panel).
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getmorefigures.php?uid=PMC2668071&req=5

pone-0005287-g003: CD45RC T cell subsets distribution in healthy individuals and ANCA patients.Peripheral blood leukocytes from 39 healthy individuals (HC), 38 patients with ANCA-associated vasculitis (AAV), and 20 patients with systemic lupus erythematosus (SLE), were stained with mAbs against CD3, CD4, CD8, CD45RC. (A) The proportion of CD45RClow CD4 T cells (left panel) and the proportion of CD45RChigh-CD45RCint-CD45RClow CD8 T cells (right three panels) are presented as box plot diagrams for each study population. The p-values were calculated using the Wilcoxon matched-pairs test; p<0.05; **, p<0.02; ***, p<0.002. (B) The proportion of CD45RClow CD4 T cells are presented according to disease subtype (WG, Wegener's granulomatosis; MPA, microscopic polyangiitis; CSS, Churg-Strauss Syndrome; RLV, renal limited vasculitis), type of ANCA specificity (MPO, myeloperoxidase; PR3, proteinase 3), renal involvement (no: no kidney disease; yes: kidney disease), and relapses (no: no relapse; yes: relapses). Data are presented as box plot diagrams for each study population. The p-values were calculated using Mann Witney U test; *p<0.05. The proportion of CD45RClow CD4 T cells are presented according to duration of disease (C, left panel). The proportion of CD45RClow CD4 T cells of 18 AAV patients (13 WG, 3 MPA, and 2 RLV patients) at 4 years interval (C, right panel).
Mentions: The analysis of CD45RC T cell subsets in the peripheral blood of patients with AAV, all in clinical remission, revealed a strong predominance of the CD45RClow subset within the CD4, but not the CD8 T cell compartment (Fig. 3A). Interestingly, we did not observe this increased proportion of CD45RClow CD4 T cells in patients with SLE, another chronic systemic autoimmune disease (Fig. 3A). The percentage of CD45RC CD4 T cells was not different between patients with the distinct disease entities of AAV (WG, MPA, CSS, and renal limited vasculitis), MPO− or PR3-ANCA, or number of relapses (Fig. 3B). Interestingly, the proportion of CD4 CD45RClow subset was significantly higher in AAV patients with renal involvement (Fig. 3B, right panel). Finally, the observed increased proportion of the CD45RClow CD4 T cells in AAV patients was not influenced by the duration of the disease and was stable during 4 year follow-up (Fig. 3C).

Bottom Line: Interestingly, AAV patients exhibit an increased proportion of CD45RC(low) CD4 T cells as compared to HC and SLE patients.In conclusion, we have shown that CD45RC expression divides human T cells in functionally distinct subsets that are imbalanced in AAV.Since this imbalance is stable over time and independent of several disease parameters, we hypothesize that this is a pre-existing immune abnormality involved in the etiology of AAV.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U563, Institut Fédératif de Recherche (IFR) 30, Hôpital Purpan and Université Paul Sabatier, Toulouse, France.

ABSTRACT
In animal models of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), the proportion of CD45RC T cell subsets is important for disease susceptibility. Their human counterparts are, however, functionally ill defined. In this report, we studied their distribution in healthy controls (HC), AAV patients and in Systemic lupus erythematous (SLE) patients as disease controls. We showed that CD45RC expression level on human CD4 and CD8 T cells identifies subsets that are highly variable among individuals. Interestingly, AAV patients exhibit an increased proportion of CD45RC(low) CD4 T cells as compared to HC and SLE patients. This increase is stable over time and independent of AAV subtype, ANCA specificity, disease duration, or number of relapses. We also analyzed the cytokine profile of purified CD4 and CD8 CD45RC T cell subsets from HC, after stimulation with anti-CD3 and anti-CD28 mAbs. The CD45RC subsets exhibit different cytokine profiles. Type-1 cytokines (IL-2, IFN-gamma and TNF-alpha) were produced by all CD45RC T cell subsets, while the production of IL-17, type-2 (IL-4, IL-5) and regulatory (IL-10) cytokines was restricted to the CD45RC(low) subset. In conclusion, we have shown that CD45RC expression divides human T cells in functionally distinct subsets that are imbalanced in AAV. Since this imbalance is stable over time and independent of several disease parameters, we hypothesize that this is a pre-existing immune abnormality involved in the etiology of AAV.

Show MeSH
Related in: MedlinePlus