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CD8 Treg Cells Inhibit B cell Proliferation and Immunoglobulin Production
  • Sudhir Gupta,
  • Houfen Su,
  • Sudhanshu Agrawal
Sudhir Gupta
University of California
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Houfen Su
University of California Irvine
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Sudhanshu Agrawal
University of California, Irvine
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Peer review status:IN REVISION

11 May 2020Submitted to Clinical & Experimental Immunology
11 May 2020Assigned to Editor
11 May 2020Submission Checks Completed
11 May 2020Reviewer(s) Assigned
03 Jun 2020Review(s) Completed, Editorial Evaluation Pending
05 Jun 2020Editorial Decision: Revise Major

Abstract

The role of CD4+ Treg in immune responses has been well established. More recently a role of CD8+ Treg in the regulation of immune responses in health and autoimmune diseases has been investigated. Furthermore, different investigators have used different markers to define CD8 Treg. Finally, regulatory effects of CD8 Treg have been studied against T cell responses; however, their role in regulating B cell proliferation and immunoglobulin production has not been evaluated. Therefore, in this study we examined the effect of two types of CD8 Treg on B cell proliferation and immunoglobulin production. Methods: Purified CD8+ T cells were activated with anti-CD3/CD28 for 48 hours and then sorted into two different types of CD8 Treg as defined by two different sets of markers, CD8+CD183+CCR7+CD45RA-, and CD8+CD183+CD25highCD278+. Purified B cells were co-cultured with sorted CD8 Treg at 1:1, 1:1/2, 1:1/4 ratios, and activated with anti-CD40 and CpG. B cell proliferation was assessed by CFSE dye dilution assay and immunoglobulin production by ELISA assay. Results: Our data show CD183+CCR7+CD45RA- CD8 T reg significantly inhibited B cell proliferation and inhibited IgM and IgG production but not of IgA production at 1:1 ratio only. However, CD183+CD25highCD278+ CD8 Treg inhibited significantly B cell proliferation at 1:1 and 1:1/2 ratio and IgM, IgG, and IgA production at all ratios. In Conclusion, CD8 Treg regulate B cell responses, and CD183+CD25highCD278+ CD8 Treg are more powerful regulators of B cell proliferation and Immunoglobulin production than CD183+CCR7+CD45RA- CD8 Treg.