| First Author | Götlind YY | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 9 | Pages | e25073 |
| PubMed ID | 21966415 | Mgi Jnum | J:177658 |
| Mgi Id | MGI:5295798 | Doi | 10.1371/journal.pone.0025073 |
| Citation | Gotlind YY, et al. (2011) CD4+FoxP3+ regulatory T cells from Galphai2-/- mice are functionally active in vitro, but do not prevent colitis. PLoS One 6(9):e25073 |
| abstractText | BACKGROUND: Mice deficient in the inhibitory G protein subunit Galphai2 spontaneously develop a T helper 1 dominated colitis. We examined whether a defect in CD4(+)FoxP3(+) regulatory T cells (Treg) underpins the pathogenesis of colitis in the Galphai2(-/-) (Galphai2-deficient) colitis model. METHODOLOGY/PRINCIPAL FINDINGS: Using flow cytometry, we found that thymus and colonic lamina propria, but not spleen and mesenteric lymph nodes, of colitic Galphai2(-/-) mice contained increased frequencies of Treg, whereas FoxP3 expression intensity was similar in Galphai2(-/-) compared to Galphai2(+/-) or Galphai2(+/+) wild type (WT) mice. The frequency of CD4(+)FoxP3(+) T cells expressing CD103 was significantly increased in Galphai2(-/-) compared to WT mice. Treg in colons from WT mice clustered in the T cell areas of colonic lymphoid patches (CLP), with relatively few Treg in the lamina propria, as demonstrated by immunohistochemistry. In Galphai2(-/-) mice, CLP were not observed but lamina propria Treg were increased in number and frequency within the CD4(+) infiltrate, compared to WT mice. Using an in vitro co-culture system and flow cytometric analysis of cell division we could demonstrate that the in vitro suppressive function of WT and Galphai2(-/-) CD4(+)FoxP3(+) regulatory T cells (WT-Treg and KO-Treg) was indistinguishable, but that T effector cells (CD4(+)25(-) T cells) from Galphai2(-/-) mice were less readily suppressed than WT effectors (WT-Teff) by Treg from either source. However, neither WT nor Galphai2(-/-) Treg was able to suppress colitis induced by adoptive transfer of Galphai2(-/-) effector T cells (KO-Teff) to RAG2(-/-) recipients. The enhanced inflammatory activity of Galphai2(-/-) effectors was accompanied by increased expression of an effector/memory T cell phenotype and increased cytokine secretion, especially IL-4, IL-6 and IFN-gamma. CONCLUSIONS: There is an increased frequency of Galphai2(-/-) Treg in the colon, and they demonstrate no endogenous functional defect. However, Galphai2(-/-) T effector cells are dramatically less susceptible to suppression in vitro, and in vivo, despite increased effective numbers of Treg, they cannot prevent disease. |
