Acute myelogenous leukemia blasts as accessory cells during in vitro T lymphocyte activation

The ability of acute myelogenous leukemia (AML) blasts to mediate costimula tory signals during T lymphocyte activation was investigated in an experime ntal model where monoclonal T cell populations were stimulated with standar dized activation signals (anti-CD3, anti-CD2, and anti-CD28 monoclonal anti bodies and phytohemagglutinin). Proliferative T cell responses were detecte d for all AML patients (n = 16) when irradiated leukemia blasts were used a s accessory cells during activation, T cell cytokine release was also obser ved for all patients when nonirradiated AML accessory cells were used, and for most patients a broad cytokine response (interleukin (IL) 2, IL4, IL10, IL13, and interferon-gamma) was detected. However, both T cell proliferati on and cytokine release showed a wide variation among AML patients, and T c ell responsiveness was in addition dependent both on the nature of the acti vation signal and on differences between individual T cell clones. The acce ssory cell function of AML blasts showed no correlation with the release of any single immunomodulatory soluble mediator (IL1 beta, IL6, TNF-alpha, so luble IL2 receptors) or the expression of any particular adhesion/costimula tory membrane molecule (CD54, CD58, CD80, and CD86) by the blasts. However, blocking studies with anti-CD58 and anti-CD80/86 monoclonal antibodies dem onstrated that both pathways can be involved when AML blasts are used as ac cessory cells, but the relative importance and the Anal effects of signalin g through these pathways differ between AML populations. Although there is a wide interpatient variation, we conclude that for a majority of patients the native AML blasts can mediate adequate costimulatory signals needed for accessory cell-dependent T cell activation. (C) 2000 Academic Press.