A T cell subtype with the CD4+CD25-FoxP3+ phenotype was recently described. We aimed to investigate the frequency of these cells and their ability to produce cytokines in tumor-draining lymph nodes from patients with breast cancer (BC).
Mononuclear cells from lymph nodes of 20 patients with BC were activated and stained for appropriate markers. The cells were assayed with four-color flow cytometry.
A very small fraction of CD4+CD25-FoxP3+ cells produced cytokines at levels that were significantly lower than in the regulatory (CD4+CD25+FoxP3+) and effector cell (CD4+CD25+FoxP3-) subpopulations. The expression of IFNγ and IL-2 in the CD4+CD25-FoxP3+ subset was significantly higher than in Treg cells, but lower than in the effector subset. Conversely, IL-22 expression in Treg cells was significantly higher than in the CD4+CD25-FoxP3+ subpopulation. The expression of IL-10 in the CD4+CD25-FoxP3+ subset was also significantly higher than in effector cells.
We suggest that CD4+CD25-FoxP3+ cells in patients with BC are exhausted cells with an intermediate phenotype between effector and regulatory cells.