Regulatory T cells (Treg) from B cell deficient (B-/-) mice are more effective at suppressing spontaneous autoimmune thyroiditis than WT Treg (115.15)

Abstract

Abstract NOD.H-2h4 mice given NaI in their water develop SAT with chronic inflammation of the thyroid by T and B cells. B-/- mice are resistant to SAT, but develop SAT after transient depletion of Treg by anti-CD25. After Treg depletion, Treg in B-/- mice take longer to repopulate than WT Treg. WT Treg have fewer FoxP3 low cells than B-/- Treg, suggesting they may have different suppressive capacities. B-/- mice have more FoxP3+ Treg, and a more activated phenotype than WT Treg with higher CD25, TGFβ, and CD44 expression, and lower CD62L and TNFR II p75. CD28-/-B-/- NOD.H2-4 mice have very few CD4+CD25+FoxP3+ Treg. We established a transfer model using splenocytes from CD28-/-B-/- mice (effector cells) cultured with or without sorted Treg from FoxP3GFP WT or B-/- mice. After transfer to mice lacking T cells, mice given Treg from B-/- mice developed significantly lower SAT severity than mice given Treg from WT mice. Although few Treg were detected at the end of culture, recipients given either WT or B-/- Treg had comparable numbers of splenic Treg 8 wks after transfer. The data herein suggests that despite being present in similar numbers both after culture and in vivo at the peak of disease, Treg that develop in B-/- mice are more effective at suppressing SAT than those in WT mice. In B-/- mice, a lack of B cells as APC during initiation of SAT may lead to preferential activation of Treg, resulting in reduced effector T cell activation and lack of SAT.