CD49d^high (integrin alpha4) innate-memory CD4⁺ T cells in the peritoneal cavity has been reported in the mouse. These cells contribute to immunoglobulin production by both B1 cells in the peritoneal cavity and splenic B2 cells. Here, we investigated whether this type of innate-memory CD4⁺ T cells are also present and play similar roles in humans.
Adult peritoneal lavage fluid, spleen, and peripheral blood cells as well as umbilical cord blood cells were obtained and analyzed. Human B1 cells (CD20⁺CD27⁺CD43⁺) were isolated and co-cultured with CD49d^highCD4⁺ T cells or CD49d^lowCD4⁺ T cells to evaluate helper function of innate-memory T cells for immunoglobulin secretion.
In contrast to mouse where CD49d^highCD4⁺ T cells were found only in the peritoneum, CD49d^highCD4⁺ T cells were found in human peritoneum, spleen and blood. Among them, CD49d^highCD4⁺ T cells were most common in the peritoneum. The CD49d^highCD4⁺ T cells showed higher expression levels of PD-1, ICOS-1, CXCR3, and CD44 than CD49d^lowCD4⁺ T cells, while their expression levels of CD62L and CCR7 were lower. CD49d^highCD4⁺ T cells had higher proliferative capacity and secreted higher levels of IFN-g, TNF-a, IL-2, and IL-21 than CD49d^lowCD4⁺ T cells. When umbilical cord blood was analyzed, CD49d^highCD4⁺ T cells were present in a low proportion; however the expression levels of CD44, CD62L, CD5 were similar as in adult blood. In mice, CD49d can form complex with integrin beta1 and beta7, and these results are identical in human CD49d. Human CD49d^high CD4⁺ T cells were found to specifically increase the secretion of immunoglobulin in human B1 cells, consistent with the role of CD49d^highCD4⁺ T cells found in mouse.
In summary, CD49d^highCD4⁺ T cells are present in human peritoneum, spleen, and blood. They showed similar innate-memory phenotypes that were identified in mouse, and helped immunoglobulin production by B1 cells.