The mechanisms by which T-cell costimulatory molecules enhance the activation of naive and/or memory T cells are under investigation. Studies have demonstrated that both murine naive CD4+ and CD8+ T cells actually acquire the costimulatory molecule B7-1 from antigen-presenting cells (APCs) after activation. This phenomenon was demonstrated using B7-1/B7-2 knockout mice; moreover, no B7-1 mRNA could be detected in T cells that had acquired B7-1. The amount of acquisition of B7-1 by T cells was shown to be directly related to both (a) the strength of signal 1 and (b) the amount of B7-1 on the APC. Studies also indicate that naive T cells, following acquisition of B7-1 from APCs, are themselves capable of acting as APCs. Moreover, results indicate that memory T cells that have acquired B7-1 from APCs can undergo apoptosis in the presence of increased levels of signal 1. These findings thus indicate that both immunostimulatory and immune regulatory functions can occur as a result of B7-1 acquisition by different T- cell populations. The interaction between CD28 on T cells and CD80 on APCs intensifies the linkage between TCR and MHC at the site of contact between T cells and APCs. We have also demonstrated that during human T cell/human APC interaction, the autologous or allogeneic human CD4(+) T cells become positive for the detection of CD80 at an early stage of activation (24 h). This detection of CD80 is attributable to the acquisition of CD80 from APCs, as opposed to the up-regulation of endogenous CD80, as demonstrated by CD4(+) T cells treated with cyclohexamide. Furthermore, no CD80 mRNA could be detected at 24 h in T cells that had acquired CD80 from APCs. CD80 acquisition by T cells from APCs was enhanced upon TCR engagement. The amount of CD80 acquisition by CD4(+) T cells was shown to be related to the expression of CD80 on APCs. Using soluble fusion proteins (soluble CTLA-4, CD28, and CD80) to block either CD28 on the surface of T cells or CD80 on the surface of APCs, it was demonstrated that CD80 acquisition by T cells is mediated through its receptors, possibly CD28 interaction. Moreover, we have demonstrated that T cells that have acquired CD80 have the ability to stimulate other T cells. These data thus suggest that CD80 acquisition by human T cells might play a role in the immunoregulation of T cell responses
