Serosal Cavities Contain Two Populations of Innate-like integrin α4 high CD4 + T Cells, Integrin α4β1 + α6β1 + α4β7 - and α4β1 + α6β1 - α4β7 + Cells.

We previously reported peritoneal innate-like integrin alpha 4 (CD49d)(high)CD4(+) T cells that provided help for B-1a cells. Here we analyzed the expression of various integrin chains on the peritoneal and pleural integrin alpha 4(high)CD4(+) T cells and investigated the functional heterogeneity of the subpopulations based on the integrin expression. Pleural cavity contained a lower ratio of integrin alpha 4(high)CD4(+) T cells to integrin alpha 4(low)CD4(+) T cells than peritoneal cavity, but the pleural integrin alpha 4(high)CD4(+) T cells have the same characteristics of the peritoneal integrin alpha 4(high)CD4(+) T cells. Most of integrin alpha 4(high)CD4(+) T cells were integrin beta 1(high)beta 7(-), but a minor population of integrin alpha 4(high)CD4(+) T cells was integrin beta 1(+)beta 7(+). Interestingly, the integrin alpha 4(high)beta 1(high)beta 7(-) CD4(+) T cells expressed high levels of integrin alpha 4 beta 1 and alpha 6 beta 1, whereas integrin alpha 4(high)beta 1(+)beta 7(+) CD4(+) T cells expressed high levels of integrin alpha 4 beta 1 and alpha 4 beta 7, suggesting an alternative expression of integrin alpha 6 beta 1 or alpha 4 beta 7 in combination with alpha 4 beta 1 in respective major and minor populations of integrin alpha 4(high)CD4(+) T cells. The minor population, integrin alpha 4(high)beta 1(+)beta 7(+) CD4(+) T cells, were different from the integrin alpha 4(high)beta 1(high)beta 7CD4(+) T cells in that they secreted a smaller amount of Th1 cytokines upon stimulation and expressed lower levels of Th1-related chemokine receptors CCR5 and CXCR3 than the integrin alpha 4(high)beta 1(high)beta 7(-)CD4(+) T cells. In summary, the innate-like integrin alpha 4(high)CD4(+) T cells could be divided into 2 populations, integrin alpha 4 beta 1(+)alpha 6 beta 1(+)alpha 4 beta 7(-) and alpha 4 beta 1(+)alpha 6 beta 1(-)alpha 4 beta 7(+) cells. The functional significance of serosal integrin alpha 4 beta 7(+) CD4(+) T cells needed to be investigated especially in view of mucosal immunity.