Choice of resident costimulatory molecule can influence cell fate in human naïve CD4+ T cell differentiation

With antigen stimulation, naïve CD4+ T cells differentiate to several effector or memory cell populations, and cytokines contribute to differentiation outcome. Several proteins on these cells receive costimulatory signals, but a systematic comparison of their differential effects on naïve T cell differentiation has not been conducted. Two costimulatory proteins, CD28 and ICAM-1, resident on human naïve CD4+ T cells were compared for participation in differentiation. Under controlled conditions, and with no added cytokines, costimulation through either CD3+CD28 or CD3+CAM-1 induced differentiation to T effector and T memory cells. In contrast, costimulation through CD3+ICAM-1 induced differentiation to Treg cells whereas costimulation through CD3+CD28 did not.

► Costimulatory molecules participate in differentiation of human naïve CD4+ T cells. ► CD28 and ICAM-1 are known costimulators; both cause differentiation to memory T cells. ► ICAM-1 did but CD28 did not induce differentiation to Treg cells capable of suppression. ► IL-2 was required but IL-10 and TGFβ were not required for the differentiation. ► Choice of costimulatory molecule can affect cell fate in naïve T cell differentiation.