The effector component of the cytotoxic T-lymphocyte response has a biphasic pattern after burn injury

Citation
Jp. Hunt et al., The effector component of the cytotoxic T-lymphocyte response has a biphasic pattern after burn injury, J SURG RES, 80(2), 1998, pp. 243-251
Citations number
27
Categorie Soggetti
Surgery,"Medical Research Diagnosis & Treatment
Journal title
JOURNAL OF SURGICAL RESEARCH
ISSN journal
00224804 → ACNP
Volume
80
Issue
2
Year of publication
1998
Pages
243 - 251
Database
ISI
SICI code
0022-4804(199812)80:2<243:TECOTC>2.0.ZU;2-Z
Abstract
Introduction. Burn injury delays allograft rejection and impairs the host d efense against infection. These functions are mediated via the cytotoxic T- lymphocyte (CTL) response. The CTL response is divided into antigen recogni tion/processing and effector phases. Presensitization allows selective anal ysis of changes, induced by burn injury, in the effector limb of the CTL re sponse in relation to time and burn size. Methods. Anesthetized CBA mice were primed with either a flank allograft fr om C57BL/6 (B6) mice or an autograft (negative control). Five weeks after g rafting, animals were anesthetized and received either a 0, 20, or 40% burn . Spleens were harvested 3, 7, 10, and 14 days after burn injury (n = 96), cocultured with B6 stimulator splenocytes, and assessed for CTL response to radiolabeled allogeneic targets in a Cr-51 release assay. In experiment 2, spleens were harvested from unburned and 40% burned animals on Postburn Da ys 3 and 14. After triple staining, cells were analyzed by flow cytometry f or CD4, CD8, and CD25 antigens. In experiment 3, splenocytes from 0 and 40% burned animals on Postburn Days 3 and 14, were cocultured with B6 stimulat ors for 5 days. Supernatants were evaluated for interleukin (IL)-2, IL-5, a nd interferon-gamma (IFN-gamma) using ELISA. Results. The CTL response for 20 and 40% burned animals decreased 3 days po stburn (-11.9 and -30.1%, P < 0.05), returned to baseline in 7-10 days, and was increased by 14 days postburn (15.8 and 22.6%, P < 0.05). The T-helper lymphocyte population (CD4) from 40% burn animals was significantly decrea sed on Postburn Days 3 and 14 (10.12 +/- 0.45% vs 11.78 +/- 0.29% and 10.19 +/- 0.24% vs 14.21 +/- 0.97%, respectively, P < 0.05). The CTL effector (C D8) splenocyte population was significantly higher in the burned animals on Postburn Day 14 (4.55% vs 3.71%, P < 0.05). On Postburn Day 3, average IL- 5 production was higher in the burned animals (1.80 pg/ml vs 0.59 pg/ml, re spectively, P < 0.05). The burn group, on Postburn Days 3 and 14, showed a decrease in mean IL-2 production (212.81 pg/ml vs 263.6 pg/ml and 342.7 pg/ ml vs 421.4 pg/ml, respectively, P < 0.05). Mean IFN-gamma production on Po stburn Days 3 and 14 was decreased in burned mice (263.75 pg/ml vs 285.57 p g/ml and 218.16 pg/ml vs 263.42 pg/ml, P < 0.05). Conclusions. Burn injury impairs the effector limb of the CTL response as a function of burn size in the immediate postburn period. CTL activity retur ns to baseline within 7-10 days postburn and has a rebound increase by Day 14. Early CTL suppression, after burn injury, may be due to a decrease in t he T-helper subpopulation. The late increase in cytotoxicity may be seconda ry to an increase in the effector CTL population in the late postburn perio d. Burn injury causes a T-helper-2 phenotype as demonstrated by depressed I L-2 and IFN-gamma production and increased IL-5 production. (C) 1998 Academ ic Press.