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Apoptosis of Fashigh CD4+ synovial T cells by borrelia-reactive Fas-ligand(high) gamma delta T cells in Lyme arthritis.

Vincent MS, Roessner K, Lynch D, Wilson D, Cooper SM, Tschopp J, Sigal LH, Budd RC - J. Exp. Med. (1996)

Bottom Line: Synovial fluid lymphocytes from patients with Lyme arthritis contain a large proportion of gamma delta cells that proliferate in response to the causative spirochete, Borrelia burgdorferi.Furthermore, synovial gamma delta T cell clones express elevated and sustained levels of the ligand for Fas (APO-1, CD95) compared to alpha beta T cells, and induce apoptosis of Fashigh CD4+ synovial lymphocytes.The findings suggest that gamma delta T cells contribute to defense in human infections, as well as manifest an immunoregulatory function at inflammatory sites by a Fas-dependent process.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington 05405-0068, USA.

ABSTRACT
The function of the minor subset of T lymphocytes bearing the gamma delta T cell antigen receptor is uncertain. Although some gamma delta T cells react to microbial products, responsiveness has only rarely been demonstrated toward a bacterial antigen from a naturally occurring human infection. Synovial fluid lymphocytes from patients with Lyme arthritis contain a large proportion of gamma delta cells that proliferate in response to the causative spirochete, Borrelia burgdorferi. Furthermore, synovial gamma delta T cell clones express elevated and sustained levels of the ligand for Fas (APO-1, CD95) compared to alpha beta T cells, and induce apoptosis of Fashigh CD4+ synovial lymphocytes. The findings suggest that gamma delta T cells contribute to defense in human infections, as well as manifest an immunoregulatory function at inflammatory sites by a Fas-dependent process.

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High level expression of surface Fas by synovial  CD4+ cells. Mononuclear cells  from freshly isolated Lyme arthritis synovial fluid or PBL were  immunofluorescently stained for  surface expression of Fas and either CD4, CD8, or γδ. Number  insets represent percent of positively stained cells. Only the  CD4+ subset of synovial fluid  cells contains a large proportion  of Fashigh cells.
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Figure 3: High level expression of surface Fas by synovial CD4+ cells. Mononuclear cells from freshly isolated Lyme arthritis synovial fluid or PBL were immunofluorescently stained for surface expression of Fas and either CD4, CD8, or γδ. Number insets represent percent of positively stained cells. Only the CD4+ subset of synovial fluid cells contains a large proportion of Fashigh cells.

Mentions: Synovial fluid lymphocytes were examined from seven patients with Lyme arthritis of 6 mo to 3.2-y duration. These contained a predominance of CD4+ over CD8+ αβ T cells in only four of seven cases (Fig. 1 A, Table 1), compared to a consistent CD4 predominance in PBL. Also present in the synovial mononuclear cells was a remarkable percentage of γδ T cells (18.9 ± 6.8%) (Fig. 1 A, Table 1), compared to ∼1–5% in PBL (Reference 1 and see Fig. 3). The synovial γδ population was largely devoid of surface CD4, and only a minor proportion (∼20% on average) expressed low to intermediate levels of CD8 (Fig. 1 B). In addition, whereas γδ T cells from PBL express predominantly the Vδ2 gene product (33), Lyme arthritis synovial fluid γδ cells were primarily of the Vδ1 subset, with lesser proportions of Vδ2 and Vδ3 cells. This was determined by both flow cytometry using Vδ-specific antibodies (Fig. 1 A), and semi-quantitative PCR using specific Vδ primers (Fig. 2).


Apoptosis of Fashigh CD4+ synovial T cells by borrelia-reactive Fas-ligand(high) gamma delta T cells in Lyme arthritis.

Vincent MS, Roessner K, Lynch D, Wilson D, Cooper SM, Tschopp J, Sigal LH, Budd RC - J. Exp. Med. (1996)

High level expression of surface Fas by synovial  CD4+ cells. Mononuclear cells  from freshly isolated Lyme arthritis synovial fluid or PBL were  immunofluorescently stained for  surface expression of Fas and either CD4, CD8, or γδ. Number  insets represent percent of positively stained cells. Only the  CD4+ subset of synovial fluid  cells contains a large proportion  of Fashigh cells.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196368&req=5

Figure 3: High level expression of surface Fas by synovial CD4+ cells. Mononuclear cells from freshly isolated Lyme arthritis synovial fluid or PBL were immunofluorescently stained for surface expression of Fas and either CD4, CD8, or γδ. Number insets represent percent of positively stained cells. Only the CD4+ subset of synovial fluid cells contains a large proportion of Fashigh cells.
Mentions: Synovial fluid lymphocytes were examined from seven patients with Lyme arthritis of 6 mo to 3.2-y duration. These contained a predominance of CD4+ over CD8+ αβ T cells in only four of seven cases (Fig. 1 A, Table 1), compared to a consistent CD4 predominance in PBL. Also present in the synovial mononuclear cells was a remarkable percentage of γδ T cells (18.9 ± 6.8%) (Fig. 1 A, Table 1), compared to ∼1–5% in PBL (Reference 1 and see Fig. 3). The synovial γδ population was largely devoid of surface CD4, and only a minor proportion (∼20% on average) expressed low to intermediate levels of CD8 (Fig. 1 B). In addition, whereas γδ T cells from PBL express predominantly the Vδ2 gene product (33), Lyme arthritis synovial fluid γδ cells were primarily of the Vδ1 subset, with lesser proportions of Vδ2 and Vδ3 cells. This was determined by both flow cytometry using Vδ-specific antibodies (Fig. 1 A), and semi-quantitative PCR using specific Vδ primers (Fig. 2).

Bottom Line: Synovial fluid lymphocytes from patients with Lyme arthritis contain a large proportion of gamma delta cells that proliferate in response to the causative spirochete, Borrelia burgdorferi.Furthermore, synovial gamma delta T cell clones express elevated and sustained levels of the ligand for Fas (APO-1, CD95) compared to alpha beta T cells, and induce apoptosis of Fashigh CD4+ synovial lymphocytes.The findings suggest that gamma delta T cells contribute to defense in human infections, as well as manifest an immunoregulatory function at inflammatory sites by a Fas-dependent process.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington 05405-0068, USA.

ABSTRACT
The function of the minor subset of T lymphocytes bearing the gamma delta T cell antigen receptor is uncertain. Although some gamma delta T cells react to microbial products, responsiveness has only rarely been demonstrated toward a bacterial antigen from a naturally occurring human infection. Synovial fluid lymphocytes from patients with Lyme arthritis contain a large proportion of gamma delta cells that proliferate in response to the causative spirochete, Borrelia burgdorferi. Furthermore, synovial gamma delta T cell clones express elevated and sustained levels of the ligand for Fas (APO-1, CD95) compared to alpha beta T cells, and induce apoptosis of Fashigh CD4+ synovial lymphocytes. The findings suggest that gamma delta T cells contribute to defense in human infections, as well as manifest an immunoregulatory function at inflammatory sites by a Fas-dependent process.

Show MeSH
Related in: MedlinePlus