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
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.