Alterations in CD8αβ and CD8αα T Cell Levels in Patients With Rheumatoid Arthritis
Study Details
Study Description
Brief Summary
To evaluate the changes in the frequencies of circulating CD4+ and CD4- T cells expressing CD8αα and CD8αβ in peripheral blood of RA patients in comparison with healthy controls. Also, to correlate circulating and synovial fluid levels of these cells with disease activity score (DAS28) and other indices of disease severity.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease of the joints . CD4+ T cells are predominant in the synovial tissue with increased number of CD8 effector and memory T cells in synovial fluid and tissue of RA patients . CD8 functions as a dimer; including homodimer CD8αα and heterodimer CD8αβ . CD8αβ is a superior T-cell co-receptor that enhances functional avidity, CD8αα functions as a TCR corepressor to negatively regulate T cell activation . CD8αα T cells are found in human intestine and peripheral blood . CD8αα T cells increased markedly in the lesions of psoriasis where they played a pro-inflammatory role . The lower percentage of CD8αα+ mucosa associated-invariant T (MAIT) cells was found to be associated with MAIT cell dysfunction in gut immunity in necrotizing enterocolitis patients . T cells express the CD8β chain either at a high (CD8βhigh) or low density (CD8βlow ). There was a relative increase in CD8βlow cells in patients with SLE which were associated with an increased disease activity . Double positive (DP) T lymphocytes, include CD4CD8αβhigh and CD4CD8αα T cell subsets in the human blood . DP8α cells decreased in the blood and colonic mucosa of patients with inflammatory bowel disease compared with healthy individuals . CD4CD8αβhigh T cells are present at higher frequencies in some auto-immune diseases . Whether CD8αα or CD8αβ T cells contribute to the pathogenesis of RA, has not been clarified so far. investigators hypothesize that, an alteration in the frequency and distribution of these T cell subsets in RA patients might be associated with disease activity
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| patients group . Inclusion criteria: Patients with RA who fulfilled the 2010 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) revised criteria for RA (1 Patients having knee effusion . Exclusion criteria: Patients with autoimmune diseases other than RA. Patients or controls with tumors, infections, or other severe organ damage. |
Diagnostic Test: flow cytometry
Levels of circulating and synovial fluid CD4+ and CD4- T cells expressing CD8αα and CD8αβ will be assessed by flow cytometry using fluorochrome-labelled monoclonal antibodies against CD3, CD4, CD8α and CD8β surface markers. Levels of the following cells will be assessed:
CD3+CD4-CD8αα+
CD3+CD4-CD8α+CD8βlow
CD3+CD4-CD8α+CD8βhigh
CD3+CD4+CD8αβhigh
CD3+CD4+CD8αα+
|
| controls group healthy subjects |
Diagnostic Test: flow cytometry
Levels of circulating and synovial fluid CD4+ and CD4- T cells expressing CD8αα and CD8αβ will be assessed by flow cytometry using fluorochrome-labelled monoclonal antibodies against CD3, CD4, CD8α and CD8β surface markers. Levels of the following cells will be assessed:
CD3+CD4-CD8αα+
CD3+CD4-CD8α+CD8βlow
CD3+CD4-CD8α+CD8βhigh
CD3+CD4+CD8αβhigh
CD3+CD4+CD8αα+
|
Outcome Measures
Primary Outcome Measures
- detection the level of circulating CD4+ and CD4- T cells expressing CD8αα and CD8αβ in peripheral blood and synovial fluid aspirates of RA patients. [baseline]
The frequencies of circulating CD4+ and CD4- T cells expressing CD8αα and CD8αβ in RA patients in comparison with healthy controls. and Comparing the frequencies of these cells between peripheral blood and synovial fluid aspirates of RA patients.
Secondary Outcome Measures
- numbers of patients have remission [baseline]
To assess the relation between the level of these cells and numbers of patients have remission
Eligibility Criteria
Criteria
Inclusion Criteria:
- Patients with RA who fulfilled the 2010 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) revised criteria for RA (12).
Patients having knee effusion .
Exclusion Criteria:
- Patients with autoimmune diseases other than RA. Patients or controls with tumors, infections, or other severe organ damage.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Assiut University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
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- Parel Y, Chizzolini C. CD4+ CD8+ double positive (DP) T cells in health and disease. Autoimmun Rev. 2004 Mar;3(3):215-20. doi: 10.1016/j.autrev.2003.09.001.
- Qiu Y, Peng K, Liu M, Xiao W, Yang H. CD8alphaalpha TCRalphabeta Intraepithelial Lymphocytes in the Mouse Gut. Dig Dis Sci. 2016 Jun;61(6):1451-60. doi: 10.1007/s10620-015-4016-y. Epub 2016 Jan 14.
- Sarrabayrouse G, Bossard C, Chauvin JM, Jarry A, Meurette G, Quevrain E, Bridonneau C, Preisser L, Asehnoune K, Labarriere N, Altare F, Sokol H, Jotereau F. CD4CD8alphaalpha lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease. PLoS Biol. 2014 Apr 8;12(4):e1001833. doi: 10.1371/journal.pbio.1001833. eCollection 2014 Apr.
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- Tian J, Yan C, Jiang Y, Zhou H, Li L, Shen J, Wang J, Sun H, Yang G, Sun W. Peripheral and intestinal mucosal-associated invariant T cells in premature infants with necrotizing enterocolitis. Front Pharmacol. 2022 Sep 14;13:1008080. doi: 10.3389/fphar.2022.1008080. eCollection 2022.
- Werwitzke S, Tiede A, Jacobs R, Zielinska-Skowronek M, Buyny S, Schmidt RE, Witte T. CD8alpha+beta(low) effector T cells in systemic lupus erythematosus. Scand J Immunol. 2008 May;67(5):501-8. doi: 10.1111/j.1365-3083.2008.02093.x.
- Wu J, Zhou C, Robertson J, Weng CC, Meistrich ML, Tailor RC, Lou YH. Identification of a bone marrow-derived CD8alphaalpha+ dendritic cell-like population in inflamed autoimmune target tissue with capability of inducing T cell apoptosis. J Leukoc Biol. 2010 Nov;88(5):849-61. doi: 10.1189/jlb.0310133. Epub 2010 Jul 13.
- Zhang F, Wei K, Slowikowski K, Fonseka CY, Rao DA, Kelly S, Goodman SM, Tabechian D, Hughes LB, Salomon-Escoto K, Watts GFM, Jonsson AH, Rangel-Moreno J, Meednu N, Rozo C, Apruzzese W, Eisenhaure TM, Lieb DJ, Boyle DL, Mandelin AM 2nd; Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium; Boyce BF, DiCarlo E, Gravallese EM, Gregersen PK, Moreland L, Firestein GS, Hacohen N, Nusbaum C, Lederer JA, Perlman H, Pitzalis C, Filer A, Holers VM, Bykerk VP, Donlin LT, Anolik JH, Brenner MB, Raychaudhuri S. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019 Jul;20(7):928-942. doi: 10.1038/s41590-019-0378-1. Epub 2019 May 6.
- Zhang YY, Lin YT, Wang L, Sun XW, Dang EL, Xue K, Zhang WG, Zhang KM, Wang G, Li B. CD8alphaalpha+T cells exert a pro-inflammatory role in patients with psoriasis. Skin Health Dis. 2021 Nov 16;1(4):e64. doi: 10.1002/ski2.64. eCollection 2021 Dec.
- T cells in RA