Postburn constitutional changes in T-cell reactivity occur in CD8+ rather than in CD4+ cells.
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+ cells during the immediate posttraumatic course compared with controls, whereas the number of CD4+ 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+ cell with a nearly fivefold elevated production on day 5 (7.2 +/- 2.6%) versus 1.5 +/- 0.4% in controls. Although CD8+ cells are also capable of enhancing their IFN-gamma synthesis under stress by about 60%, the CD4+ IFN-gamma release remained largely unchanged.


CONCLUSIONS
Our data corroborate that major burn trauma will induce a significant shift of cytokine response toward the TH2 direction and demonstrate that the CD8+ rather than the CD4+ phenotype is the crucial cell for the polarization toward a TH2-driven immune response.
Zedler
S
S
Department of Surgery, Ludwig-Maximilians-University Munich, Klinikum Grosshadern, Germany.
Faist
E
E
Ostermeier
B
B
von Donnersmarck
G H
GH
Schildberg
F W
FW
D000328:Adult; D000368:Aged; D002056:Burns / Q000097:blood / Q000276:immunology*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors