Immune deficiency following thermal trauma is associated with apoptotic cell death.
Thermal injury-associated specific immune deficiency occurs despite indicators of systemic activation of the lymphoid compartment. We investigated the possibility that postburn immune failure and T cell activation are casually related through activation-induced (apoptotic) cell death. The relationship between the cellular immune response and cell mortality was examined in cultures of peripheral blood mononuclear cells (PBMC) from 14 immunosuppressed patients with extensive burns (35-90% total body surface area). Impaired cellular immunity coincided with significantly reduced cell viability as ascertained by propidium iodide staining and dye reduction assays. Following stimulation with the mitogenic lectin, phytohemagglutinin (PHA), the majority of DNA in patient cultures was fragmented, suggesting the occurrence of apoptotic cell death. Even without stimulation a portion of patient cells was apoptotic as indicated by oligonucleosomal bands on agarose gel electrophoresis. Exogenous interleukin-2 or phorbol ester markedly reduced constitutive 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 circulating lymphocytes was undergoing apoptosis on the periphery. These novel observations suggest that apoptosis may play a major role in thermal injury-related cellular immunodeficiency.
Teodorczyk-Injeyan
J A
JA
Department of Surgery, University of Toronto, Ontario, Canada.
Cembrzynska-Nowak
M
M
Lalani
S
S
Peters
W J
WJ
Mills
G B
GB
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology*; D002056:Burns / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D004249:DNA Damage / Q000276:immunology; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged