IMMUNE-DEFICIENCY FOLLOWING THERMAL TRAUMA IS ASSOCIATED WITH APOPTOTIC CELL-DEATH

Thermal injury-associated specific immune deficiency occurs despite in dicators of systemic activation of the lymphoid compartment. We invest igated the possibility that postburn immune failure and T cell activat ion are causally related through activation-induced (apoptotic) cell d eath. The relationship between the cellular immune response and cell m ortality was examined in cultures of peripheral blood mononuclear cell s (PBMC) from 14 immunosuppressed patients with extensive bums (35-90% total body surface area). Impaired cellular immunity coincided with s ignificantly reduced cell viability as ascertained by propidium iodide staining and dye reduction assays. Following stimulation with the mit ogenic lectin, phytohemagglutinin (PHA), the majority of DNA in patien t cultures was fragmented, suggesting the occurrence of apoptotic cell death. Even without stimulation a portion of patient cells was apopto tic as indicated by oligonucleosomal bands on agarose gel electrophore sis. Exogenous interleukin-2 or phorbol ester markedly reduced constit utive as well as PHA-induced DNA fragmentation. In situ demonstration of DNA strand breaks in freshly isolated patient PBMC, by a TdT-based labeling technique, confirmed that a larger fraction (up to 60%) of ci rculating lymphocytes was undergoing apoptosis on the periphery. These novel observations suggest that apoptosis may play a major role in th ermal injury-related cellular immunodeficiency.