Early Development in the Peritoneal Cavity of CD49d^high Th1 Memory Phenotype CD4⁺ T Cells with Enhanced B Cell Helper Activity

다국어 초록 (Multilingual Abstract)

<P>The Th cells that regulate peritoneal B-1 cell functions have not yet been well characterized. To address this question, we investigated peritoneal CD4<SUP>+</SUP> T cells, observed a high frequency of the conjugates of B-CD4<SUP>+</SUP> T cells in the peritoneal cavity, and identified a population of CD49d<SUP>high</SUP>CD4<SUP>+</SUP> T cells that constituted about half of all CD4<SUP>+</SUP> T cells in the peritoneal cavity, but were rarely found in other compartments. Peritoneal CD49d<SUP>high</SUP>CD4<SUP>+</SUP> T cells were CD44<SUP>high</SUP>CD62L<SUP>low</SUP>; expressed integrin α<SUB>4</SUB>β<SUB>1</SUB> and CXCR3; and rapidly secreted IFN-γ, TNF-α, and IL-2, showing features of proinflammatory Th1 cells. Peritoneal CD49d<SUP>high</SUP>CD4<SUP>+</SUP> T cells developed spontaneously, were detected at the age of 12 d, and showed stem cell–like properties. Their development was observed in mice deficient for signaling lymphocytic activation molecule-associated protein, but not in athymic nude mice and mice lacking in expression of MHC class II on thymic epithelial cells. Peritoneal CD49d<SUP>high</SUP>CD4<SUP>+</SUP> T cells were more resistant to irradiation and more sensitive to NAD-induced cell death than CD49d<SUP>low</SUP>CD4<SUP>+</SUP> T cells. Notably, peritoneal CD49d<SUP>high</SUP>CD4<SUP>+</SUP> T cells also showed some characteristics of follicular Th cells, such as the expression of programmed cell death 1, ICOS, IL-21, and CXCR5. Moreover, peritoneal CD49d<SUP>high</SUP>CD4<SUP>+</SUP> T cells enhanced the secretion of IgM Abs by B-1a cells and IgG Abs by splenic B cells. These data suggest that peritoneal CD49d<SUP>high</SUP>CD4<SUP>+</SUP> T cells may be innate-like CD4<SUP>+</SUP> T cells, which develop early and have a dual capacity to support both humoral and cellular immunity.</P>