ICOS and autoimmune disease: Additionally, activated CXCR5+CD4+TFH cells with ICOS and/or PD-1 expression can secret abundant IL-21 cytokine by themselves, and the levels of both IL-21 and IL-6 cytokines are significantly related with the frequency of circulating CXCR5+CD4+TFH cells with ICOS and/or PD-1 expression in some autoimmune diseases [17–19, 39–41].