Postburn Constitutional Changes in T-cell Reactivity Occur in CD8 sup + Rather than in CD4 sup + Cells

Abstract

Background Impairment of T-helper cell function and polarization toward T-helper 2-type cytokine synthesis have been postulated to represent a major cause for posttraumatic immunodeficiency. With a recently developed technology for intracellular cytokine measurement, a new diagnostic tool has become available to discriminate, within hours, a shift of functionality in T-cell subsets via their individual cytokine profiles. Thus, it was the objective of this study to obtain further insight into the constitutional, phenotype-dependent changes of T-helper 1 (TH1) and T-helper 2 (TH2), respectively, signature lymphokine synthesis under traumatic stress. Methods Peripheral blood mononuclear cells from 10 patients with major burn injury on day 1, 3, 5, and 7 after injury and from 15 healthy individuals were separated and incubated (5 hours) for cytokine production induced with the accessory cell-independent stimulus of ionomycin and phorbol 12-myristate 13-acetate. After fixation and permeabilization, cell samples were immunofluorescently stained for cell surface antigens (CD4 and CD8) as well as for intracellular interferon (IFN)-gamma and interleukin (IL)-4 synthesis. Results were correlated with corresponding enzyme-linked immunosorbent assay measurements of the culture supernatants. Results Phenotypic assessment of peripheral blood mononuclear cells showed a continuously diminished percentage of CD8 sup + cells during the immediate posttraumatic course compared with controls, whereas the number of CD4 sup + cells was found to be within the range of the control group. The production of IL-4, the index cytokine of TH2 cells, was excessively up-regulated (from 437.8 +/- 137.0 pg/mL on day 1 to 1,333.6 +/- 532.7 pg/mL on day 7 burns vs. 82.3 +/- 15.8 pg/mL controls), whereas the release of IFN-gamma, the index cytokine of TH1 cells, however, was only slightly increased. The predominant cellular source of IL-4 after burn trauma has been shown to be the CD8 sup + cell with a nearly fivefold elevated production on day 5 (7.2 +/- 2.6%) versus 1.5 +/- 0.4% in controls. Although CD8 sup + cells are also capable of enhancing their IFN-gamma synthesis under stress by about 60%, the CD4 sup + IFN-gamma release remained largely unchanged. Conclusion Our data corroborate that major burn trauma will induce a significant shift of cytokine response toward the TH2 direction and demonstrate that the CD8 sup + rather than the CD4 sup + phenotype is the crucial cell for the polarization toward a TH2-driven immune response.