Early Development in the Peritoneal Cavity of CD49dhigh Th1 Memory Phenotype CD4+ T Cells with Enhanced B Cell Helper Activity

Abstract

The Th cells that regulate peritoneal B-1 cell functions have not yet been well characterized. To address this question, we investigated peritoneal CD4+ T cells, observed a high frequency of the conjugates of B-CD4+ T cells in the peritoneal cavity, and identified a population of CD49dhighCD4+ T cells that constituted about half of all CD4+ T cells in the peritoneal cavity, but were rarely found in other compartments. Peritoneal CD49dhighCD4+ T cells were CD44highCD62Llow; expressed integrin α4β1 and CXCR3; and rapidly secreted IFN-γ, TNF-α, and IL-2, showing features of proinflammatory Th1 cells. Peritoneal CD49dhighCD4+ 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 CD49dhighCD4+ T cells were more resistant to irradiation and more sensitive to NAD-induced cell death than CD49dlowCD4+ T cells. Notably, peritoneal CD49dhighCD4+ 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 CD49dhighCD4+ T cells enhanced the secretion of IgM Abs by B-1a cells and IgG Abs by splenic B cells. These data suggest that peritoneal CD49dhighCD4+ T cells may be innate-like CD4+ T cells, which develop early and have a dual capacity to support both humoral and cellular immunity.