SUMMARY
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, and therefore, may be used as preferred
markers for CD8 Treg.
Key Words: CD8 Treg, B cell proliferation, Immunoglobulin
production, ICOS