Evidence for intact costimulation via CD28 and CD27 molecules in hyporesponsive T cells from human immunodeficiency virus‐infected individuals

Abstract

In the activation of T cells, the primary signal is antigen‐specific and given through T cell receptor (TcR)/CD3 ligation. Furthermore, costimulatory molecules such as CD28 and CD27, provide an essential signal for activation through interaction with their ligands, present on the membrane of antigen‐presenting cells. During asymptomatic human immunodeficiency virus (HIV)‐1 infection, T cell function is progressively lost. Here, we investigated whether in the presence of impaired responses of T cells from HIV‐infected individuals to signal one, costimulation through CD28 and CD27 after interaction with their natural ligands CD80 and CD70 is intact. T cell proliferative responses to signal one in combination with CD80 or CD70 were decreased in a large fraction of asymptomatically HIV‐infected individuals. This was due to impaired responses of signal one but not to impaired responses to costimulation, since CD80 or CD70 did enhance signal one‐mediated proliferative responses to a normal extent. Moreover, in individuals with proliferative responses to signal one that were decreased to 50% of normal T cell responses, costimulation even was increased compared to controls. Our results demonstrate that in HIV‐infected individuals the response to costimulation is relatively preserved compared to responses to the first signal and point to the defect in T cells in HIV infection being primarily in the CD3/TcR‐mediated pathway.