Subpopulations of primed t helper cells in rheumatoid arthritis

Matthews, Nick; Emery, Paul; Pilling, Darrell; Akbar, Arne N.; Salmon, Mike

doi:10.1002/art.1780360505

Cited by 45 publications

(25 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As mentioned earlier, this was the only difference observed in the distribution of CD4' subsets in LIL between PBC paiients and ALD, and it must be considered significant because it is completely independent of the general expansion of the CD4^ memory subset, which was observed for tissue-infiltrating lymphocytes of both PBC and ALD patients. Results obtained with lymphocytes from the synovia of RA patients and other inflammatory joint disease patients have found a similar distribution with a real expansion of this subset (memory-2) [17,18]. This finding could be related to the pathogenesis of PBC.…”

Section: Discussionsupporting

confidence: 64%

“…An altered profile of T cells with a decreased naive (CD45RA^) subset and an increased memory/activated subpopulation (CD45RO +) has been reported previously in many autoimmune diseases [24], including multiple sclerosis, myasthenia gravis [25] and rheumatoid arthritis (RA) [17,18,26]. In most of the cases the abnormal distribution of CD4'^ T cell subsets has been noted in tissue-infiltrating lymphocytes without any change in PBL.…”

Section: Discussionmentioning

confidence: 68%

See 1 more Smart Citation

CD4+ T cell subsets defined by isoforms of CD45 in primary biliary cirrhosis

Leon

Spickett

Jones

et al. 1995

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARY Primary biliary cirrhosis (PBC) is an autoimmune condition characterized by destruction of the intrahepatic bile ducts. Autoreactive CD4+ T cells have been reported both in the peripheral circulation and in the mononuclear cell infiltrate in the affected portal tracts. In this large study we have used two‐ and three‐colour flow cytometry to determine the phenotypes of the CD4+ T cell subsets in the peripheral blood and liver‐infiltrating lymphocytes of PBC patients (n= 43), normal controls (n= 19) and patients with alcoholic cirrhosis (n= 15), according to a novel classification based on the simultaneous expression of different isoforms of CD45. In PBC patients the proportion of peripheral blood CD4+Cells possessing the CD45ROhigh RA−‘memory’ phenotype was significantly increased, and the CD45RO− RAhigh‘naive’ population was significantly decreased, compared with the two control groups. No significant differences in peripheral blood CD4+ T cell subsets were seen between patients with pre‐cirrhotic and cirrhotic PBC. A similar, but more marked, shift towards the CD45ROhigh RA−‘memory’ phenotype was seen in the liver‐infiltrating CD4+ T cells in PBC patients compared with alcoholic cirrhotics. Cells within the CD4+ memory subpopulation were further subgrouped according to expression of CD45RB, the level of expression of which has been associated with functional differences in the memory subset. In peripheral blood no differences were seen between PBC patients and controls with respect to the proportion of CD45ROhigh RBhigh and CD45ROhigh RBdim memory subsets. A statistically significant difference in the distribution of these memory subsets, with an increased memory‐2/ memory‐1 ratio was observed in the liver‐infiltrating CD4+ T cells of PBC patients compared with those from alcoholic cirrhotic patients. The potential implications of this observation are discussed.

show abstract

Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 68%

CD4+ T cell subsets defined by isoforms of CD45 in primary biliary cirrhosis

Leon

Spickett

Jones

et al. 1995

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…Ig levels are elevated in RA synovium, and disease severity is correlated with rheumatoid factor seropositivity (6,55,56). The expression of CD45RO and enrichment in CD45RB dim cells (14,57,58) suggests further that rheumatoid synovial CD4ϩ T cells have been stimulated previously, possibly multiple times (15, 16).…”

Section: Discussionmentioning

confidence: 95%

Functional CD40 ligand is expressed by T cells in rheumatoid arthritis.

MacDonald

Nishioka²,

Lipsky³

et al. 1997

J. Clin. Invest.

150

112

View full text Add to dashboard Cite

“…Following T cell activation, CD45RA isoform expression decreases with a concomitant up-regulation of CD45R0, a marker for 'activated/effector' T cells [34]. It is well established that CD45R0 + T cells can accumulate at sites of chronic inflammation, such as rheumatoid joints [35,36] and in inflammatory dermatoses [37]. Therefore, the CD45R0 + T cell subset represents an attractive target for immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Alefacept selectively promotes NK cell‐mediated deletion of CD45R0⁺ human T cells

et al. 2003

View full text Add to dashboard Cite

Modulation of the immune response using immunoglobulin fusion proteins has shown great promise for clinical immunotherapy of autoimmune diseases. Alefacept is an immunoglobulin fusion protein composed of the first extracellular domain of human LFA-3 fused to the hinge, C H 2 and C H 3 domains of human IgG 1 . Alefacept has previously been reported to inhibit T cell proliferation. Here, we analyzed the effects of alefacept on lymphocytes in vitro and characterized the role of autologous NK cells in its mechanism of action. Alefacept, but not a C H 2 binding mutant of Alefacept, inhibited CD3-induced T cell proliferation only in the presence of live NK cells, consistent with an important role for Fc + R engagement. Alefacept caused preferential depletion of CD69+ T cell subsets. Cytotoxicity assays revealed that alefacept, but not the C H 2 binding mutant, induced NK cell-mediated death of activated T cells and sorting into CD45R0 + and CD45RA + subpopulations showed that lymphocyte deletion occurred preferentially in the CD45R0 + subset. Activated CD45R0 + cells expressed higher levels of CD2 than CD45R0 -cells, providing a possible explanation for the selective targeting of this subset. Our results suggest that selective targeting of CD45R0 + T cells by NK cells represents a potential therapeutic mechanism of action of alefacept.

show abstract

Subpopulations of primed t helper cells in rheumatoid arthritis

Cited by 45 publications

References 15 publications

CD4+ T cell subsets defined by isoforms of CD45 in primary biliary cirrhosis

CD4+ T cell subsets defined by isoforms of CD45 in primary biliary cirrhosis

Functional CD40 ligand is expressed by T cells in rheumatoid arthritis.

Alefacept selectively promotes NK cell‐mediated deletion of CD45R0⁺ human T cells

Contact Info

Product

Resources

About

Subpopulations of primed t helper cells in rheumatoid arthritis

Cited by 45 publications

References 15 publications

CD4+ T cell subsets defined by isoforms of CD45 in primary biliary cirrhosis

CD4+ T cell subsets defined by isoforms of CD45 in primary biliary cirrhosis

Functional CD40 ligand is expressed by T cells in rheumatoid arthritis.

Alefacept selectively promotes NK cell‐mediated deletion of CD45R0+ human T cells

Contact Info

Product

Resources

About

Alefacept selectively promotes NK cell‐mediated deletion of CD45R0⁺ human T cells