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Mycobacterial ESAT-6 and katG are recognized by sarcoidosis CD4+ T cells when presented by the American sarcoidosis susceptibility allele, DRB1*1101.

Oswald-Richter K, Sato H, Hajizadeh R, Shepherd BE, Sidney J, Sette A, Newman LS, Drake WP - J. Clin. Immunol. (2009)

Bottom Line: We previously reported immune recognition of Mycobacterium peptides from peripheral cells of 26 sarcoidosis subjects, 24 PPD- healthy volunteers, and eight with latent tuberculosis infection.Recognition was inhibited by monoclonal antibody against HLA-DR and HLA-DQ, but not HLA-DP.Immune recognition of ESAT-6 peptide NNALQNLARTISEAG was associated with possession of DRB1*1101.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN, USA.

ABSTRACT

Introduction: Genetic associations of American sarcoidosis susceptibility implicate MHC class II allele, DRB1*1101. We previously reported immune recognition of Mycobacterium peptides from peripheral cells of 26 sarcoidosis subjects, 24 PPD- healthy volunteers, and eight with latent tuberculosis infection.

Materials and methods: In order to further link these genetic and immunologic pillars of sarcoidosis pathogenesis, we performed flow cytometry on these same subjects to identify the cells responsible for immune responses to ESAT-6 and katG peptides, followed by HLA typing to determine allelic associations with recognition.

Discussion and conclusion: Sarcoidosis CD4+ T cells were primarily responsible for the systemic responses. Recognition was inhibited by monoclonal antibody against HLA-DR and HLA-DQ, but not HLA-DP. Immune recognition of ESAT-6 peptide NNALQNLARTISEAG was associated with possession of DRB1*1101. ESAT-6 and katG presented by antigen-presenting cells expressing DRB1*1101-induced Th-1 responses from sarcoidosis T cells, thus providing a mechanistic insight for the association of HLA DRB1*1101 with sarcoidosis, and sarcoidosis T cell interaction with microbial antigens.

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Related in: MedlinePlus

CD4+ T cells are primarily responsible for the sarcoidosis systemic response to mycobacterial antigens. Flow cytometry revealed sarcoidosis CD4+ T cells were primarily responsible for peripheral IL-2 and interferon-γ production when stimulated with ESAT-6 peptides. While CD8+ T cell responses were identified by flow cytometry among subjects with latent tuberculosis, these responses were rare among sarcoidosis subjects. In one sarcoidosis subject (Sarcoidosis 6), CD4+ and CD8+ T cell responses were significantly elevated above baseline. Stimulation with katG peptide also induced strong CD4+ T cells response. A representative graph of responses to ESAT-6 and katG is shown
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Fig1: CD4+ T cells are primarily responsible for the sarcoidosis systemic response to mycobacterial antigens. Flow cytometry revealed sarcoidosis CD4+ T cells were primarily responsible for peripheral IL-2 and interferon-γ production when stimulated with ESAT-6 peptides. While CD8+ T cell responses were identified by flow cytometry among subjects with latent tuberculosis, these responses were rare among sarcoidosis subjects. In one sarcoidosis subject (Sarcoidosis 6), CD4+ and CD8+ T cell responses were significantly elevated above baseline. Stimulation with katG peptide also induced strong CD4+ T cells response. A representative graph of responses to ESAT-6 and katG is shown

Mentions: FACS Analysis Reveals that CD4+ T Cells are Primarily Responsible for the Sarcoidosis Response to Mycobacterial Antigens Previous work has demonstrated the production of IL-2 and IFN-γ by sarcoidosis PBMC in response to ESAT-6 and katG, using ELISPOT analysis [13]. Flow cytometry revealed that production of the Th-1 cytokines were primarily from CD4+ T cells. While recognition by CD4+ and CD8+ T cells was detected among some latent tuberculosis subjects (data not shown), CD4+ T cells responses were mainly detected among the sarcoidosis subjects to ESAT-6. Sarcoidosis 6 demonstrated CD4+ and CD8+ T cell responses to ESAT-6 (Fig. 1a). CD4+ T cell recognition of katG was also detected; a representative analysis of Sarcoidosis 10 is shown in Fig. 1b.Fig. 1


Mycobacterial ESAT-6 and katG are recognized by sarcoidosis CD4+ T cells when presented by the American sarcoidosis susceptibility allele, DRB1*1101.

Oswald-Richter K, Sato H, Hajizadeh R, Shepherd BE, Sidney J, Sette A, Newman LS, Drake WP - J. Clin. Immunol. (2009)

CD4+ T cells are primarily responsible for the sarcoidosis systemic response to mycobacterial antigens. Flow cytometry revealed sarcoidosis CD4+ T cells were primarily responsible for peripheral IL-2 and interferon-γ production when stimulated with ESAT-6 peptides. While CD8+ T cell responses were identified by flow cytometry among subjects with latent tuberculosis, these responses were rare among sarcoidosis subjects. In one sarcoidosis subject (Sarcoidosis 6), CD4+ and CD8+ T cell responses were significantly elevated above baseline. Stimulation with katG peptide also induced strong CD4+ T cells response. A representative graph of responses to ESAT-6 and katG is shown
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2821522&req=5

Fig1: CD4+ T cells are primarily responsible for the sarcoidosis systemic response to mycobacterial antigens. Flow cytometry revealed sarcoidosis CD4+ T cells were primarily responsible for peripheral IL-2 and interferon-γ production when stimulated with ESAT-6 peptides. While CD8+ T cell responses were identified by flow cytometry among subjects with latent tuberculosis, these responses were rare among sarcoidosis subjects. In one sarcoidosis subject (Sarcoidosis 6), CD4+ and CD8+ T cell responses were significantly elevated above baseline. Stimulation with katG peptide also induced strong CD4+ T cells response. A representative graph of responses to ESAT-6 and katG is shown
Mentions: FACS Analysis Reveals that CD4+ T Cells are Primarily Responsible for the Sarcoidosis Response to Mycobacterial Antigens Previous work has demonstrated the production of IL-2 and IFN-γ by sarcoidosis PBMC in response to ESAT-6 and katG, using ELISPOT analysis [13]. Flow cytometry revealed that production of the Th-1 cytokines were primarily from CD4+ T cells. While recognition by CD4+ and CD8+ T cells was detected among some latent tuberculosis subjects (data not shown), CD4+ T cells responses were mainly detected among the sarcoidosis subjects to ESAT-6. Sarcoidosis 6 demonstrated CD4+ and CD8+ T cell responses to ESAT-6 (Fig. 1a). CD4+ T cell recognition of katG was also detected; a representative analysis of Sarcoidosis 10 is shown in Fig. 1b.Fig. 1

Bottom Line: We previously reported immune recognition of Mycobacterium peptides from peripheral cells of 26 sarcoidosis subjects, 24 PPD- healthy volunteers, and eight with latent tuberculosis infection.Recognition was inhibited by monoclonal antibody against HLA-DR and HLA-DQ, but not HLA-DP.Immune recognition of ESAT-6 peptide NNALQNLARTISEAG was associated with possession of DRB1*1101.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN, USA.

ABSTRACT

Introduction: Genetic associations of American sarcoidosis susceptibility implicate MHC class II allele, DRB1*1101. We previously reported immune recognition of Mycobacterium peptides from peripheral cells of 26 sarcoidosis subjects, 24 PPD- healthy volunteers, and eight with latent tuberculosis infection.

Materials and methods: In order to further link these genetic and immunologic pillars of sarcoidosis pathogenesis, we performed flow cytometry on these same subjects to identify the cells responsible for immune responses to ESAT-6 and katG peptides, followed by HLA typing to determine allelic associations with recognition.

Discussion and conclusion: Sarcoidosis CD4+ T cells were primarily responsible for the systemic responses. Recognition was inhibited by monoclonal antibody against HLA-DR and HLA-DQ, but not HLA-DP. Immune recognition of ESAT-6 peptide NNALQNLARTISEAG was associated with possession of DRB1*1101. ESAT-6 and katG presented by antigen-presenting cells expressing DRB1*1101-induced Th-1 responses from sarcoidosis T cells, thus providing a mechanistic insight for the association of HLA DRB1*1101 with sarcoidosis, and sarcoidosis T cell interaction with microbial antigens.

Show MeSH
Related in: MedlinePlus