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

John P. Hunt, Curtis T. Hunter, Michelle R. Brownstein, Athina Giannopoulos, Charles Hultman, Suzan Deserres, Lyndie Bracey, Jeffrey Frelinger, Anthony A. Meyer

Research output: Contribution to journalArticle

Abstract

Introduction. Burn injury delays allograft rejection and impairs the host defense against infection. These functions are mediated via the cytotoxic T-lymphocyte (CTL) response. The CTL response is divided into antigen recognition/processing and effector phases. Presensitization allows selective analysis of changes, induced by burn injury, in the effector limb of the CTL response in relation to time and burn size. Methods. Anesthetized CBA mice were primed with either a flank allograft from C57BL/6 (B6) mice or an autograft (negative control). Five weeks after grafting, 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 51Cr release assay. In experiment 2, spleens were harvested from unburned and 40% burned animals on Postburn Days 3 and 14. After triple staining, cells were analyzed by flow cytometry for 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 stimulators for 5 days. Supernatants were evaluated for interleukin (IL)-2, IL-5, and interferon-γ (IFN-γ) using ELISA. Results. The CTL response for 20 and 40% burned animals decreased 3 days postburn (-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 decreased 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 (CD8) 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, respectively, 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-γ production on Postburn Days 3 and 14 was decreased in burned mice (263.75 pg/ml vs 285.57 pg/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 returns 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 the T-helper subpopulation. The late increase in cytotoxicity may be secondary to an increase in the effector CTL population in the late postburn period. Burn injury causes a T-helper-2 phenotype as demonstrated by depressed IL-2 and IFN-γ production and increased IL-5 production.

Original languageEnglish (US)
Pages (from-to)243-251
Number of pages9
JournalJournal of Surgical Research
Volume80
Issue number2
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Fingerprint

Cytotoxic T-Lymphocytes
Wounds and Injuries
Interleukin-5
Interferons
Interleukin-2
Allografts
Spleen
Extremities
Interleukin-2 Receptor alpha Subunit
Population
CD8 Antigens
CD4 Antigens
Inbred CBA Mouse
Autografts
Antigen Presentation
Helper-Inducer T-Lymphocytes
Flow Cytometry
Enzyme-Linked Immunosorbent Assay
Staining and Labeling
Phenotype

Keywords

  • Burn injury
  • CD4
  • CD8
  • Cytotoxic T lymphocytes
  • Effector limb
  • Interferon-γ
  • Interleukin- 5
  • Interleukin-2

ASJC Scopus subject areas

  • Surgery

Cite this

Hunt, J. P., Hunter, C. T., Brownstein, M. R., Giannopoulos, A., Hultman, C., Deserres, S., ... Meyer, A. A. (1998). The effector component of the cytotoxic T-lymphocyte response has a biphasic pattern after burn injury. Journal of Surgical Research, 80(2), 243-251. https://doi.org/10.1006/jsre.1998.5488

The effector component of the cytotoxic T-lymphocyte response has a biphasic pattern after burn injury. / Hunt, John P.; Hunter, Curtis T.; Brownstein, Michelle R.; Giannopoulos, Athina; Hultman, Charles; Deserres, Suzan; Bracey, Lyndie; Frelinger, Jeffrey; Meyer, Anthony A.

In: Journal of Surgical Research, Vol. 80, No. 2, 01.01.1998, p. 243-251.

Research output: Contribution to journalArticle

Hunt, JP, Hunter, CT, Brownstein, MR, Giannopoulos, A, Hultman, C, Deserres, S, Bracey, L, Frelinger, J & Meyer, AA 1998, 'The effector component of the cytotoxic T-lymphocyte response has a biphasic pattern after burn injury', Journal of Surgical Research, vol. 80, no. 2, pp. 243-251. https://doi.org/10.1006/jsre.1998.5488
Hunt, John P. ; Hunter, Curtis T. ; Brownstein, Michelle R. ; Giannopoulos, Athina ; Hultman, Charles ; Deserres, Suzan ; Bracey, Lyndie ; Frelinger, Jeffrey ; Meyer, Anthony A. / The effector component of the cytotoxic T-lymphocyte response has a biphasic pattern after burn injury. In: Journal of Surgical Research. 1998 ; Vol. 80, No. 2. pp. 243-251.
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title = "The effector component of the cytotoxic T-lymphocyte response has a biphasic pattern after burn injury",
abstract = "Introduction. Burn injury delays allograft rejection and impairs the host defense against infection. These functions are mediated via the cytotoxic T-lymphocyte (CTL) response. The CTL response is divided into antigen recognition/processing and effector phases. Presensitization allows selective analysis of changes, induced by burn injury, in the effector limb of the CTL response in relation to time and burn size. Methods. Anesthetized CBA mice were primed with either a flank allograft from C57BL/6 (B6) mice or an autograft (negative control). Five weeks after grafting, 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 51Cr release assay. In experiment 2, spleens were harvested from unburned and 40{\%} burned animals on Postburn Days 3 and 14. After triple staining, cells were analyzed by flow cytometry for 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 stimulators for 5 days. Supernatants were evaluated for interleukin (IL)-2, IL-5, and interferon-γ (IFN-γ) using ELISA. Results. The CTL response for 20 and 40{\%} burned animals decreased 3 days postburn (-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 decreased 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 (CD8) 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, respectively, 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-γ production on Postburn Days 3 and 14 was decreased in burned mice (263.75 pg/ml vs 285.57 pg/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 returns 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 the T-helper subpopulation. The late increase in cytotoxicity may be secondary to an increase in the effector CTL population in the late postburn period. Burn injury causes a T-helper-2 phenotype as demonstrated by depressed IL-2 and IFN-γ production and increased IL-5 production.",
keywords = "Burn injury, CD4, CD8, Cytotoxic T lymphocytes, Effector limb, Interferon-γ, Interleukin- 5, Interleukin-2",
author = "Hunt, {John P.} and Hunter, {Curtis T.} and Brownstein, {Michelle R.} and Athina Giannopoulos and Charles Hultman and Suzan Deserres and Lyndie Bracey and Jeffrey Frelinger and Meyer, {Anthony A.}",
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month = "1",
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TY - JOUR

T1 - The effector component of the cytotoxic T-lymphocyte response has a biphasic pattern after burn injury

AU - Hunt, John P.

AU - Hunter, Curtis T.

AU - Brownstein, Michelle R.

AU - Giannopoulos, Athina

AU - Hultman, Charles

AU - Deserres, Suzan

AU - Bracey, Lyndie

AU - Frelinger, Jeffrey

AU - Meyer, Anthony A.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - Introduction. Burn injury delays allograft rejection and impairs the host defense against infection. These functions are mediated via the cytotoxic T-lymphocyte (CTL) response. The CTL response is divided into antigen recognition/processing and effector phases. Presensitization allows selective analysis of changes, induced by burn injury, in the effector limb of the CTL response in relation to time and burn size. Methods. Anesthetized CBA mice were primed with either a flank allograft from C57BL/6 (B6) mice or an autograft (negative control). Five weeks after grafting, 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 51Cr release assay. In experiment 2, spleens were harvested from unburned and 40% burned animals on Postburn Days 3 and 14. After triple staining, cells were analyzed by flow cytometry for 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 stimulators for 5 days. Supernatants were evaluated for interleukin (IL)-2, IL-5, and interferon-γ (IFN-γ) using ELISA. Results. The CTL response for 20 and 40% burned animals decreased 3 days postburn (-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 decreased 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 (CD8) 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, respectively, 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-γ production on Postburn Days 3 and 14 was decreased in burned mice (263.75 pg/ml vs 285.57 pg/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 returns 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 the T-helper subpopulation. The late increase in cytotoxicity may be secondary to an increase in the effector CTL population in the late postburn period. Burn injury causes a T-helper-2 phenotype as demonstrated by depressed IL-2 and IFN-γ production and increased IL-5 production.

AB - Introduction. Burn injury delays allograft rejection and impairs the host defense against infection. These functions are mediated via the cytotoxic T-lymphocyte (CTL) response. The CTL response is divided into antigen recognition/processing and effector phases. Presensitization allows selective analysis of changes, induced by burn injury, in the effector limb of the CTL response in relation to time and burn size. Methods. Anesthetized CBA mice were primed with either a flank allograft from C57BL/6 (B6) mice or an autograft (negative control). Five weeks after grafting, 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 51Cr release assay. In experiment 2, spleens were harvested from unburned and 40% burned animals on Postburn Days 3 and 14. After triple staining, cells were analyzed by flow cytometry for 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 stimulators for 5 days. Supernatants were evaluated for interleukin (IL)-2, IL-5, and interferon-γ (IFN-γ) using ELISA. Results. The CTL response for 20 and 40% burned animals decreased 3 days postburn (-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 decreased 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 (CD8) 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, respectively, 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-γ production on Postburn Days 3 and 14 was decreased in burned mice (263.75 pg/ml vs 285.57 pg/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 returns 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 the T-helper subpopulation. The late increase in cytotoxicity may be secondary to an increase in the effector CTL population in the late postburn period. Burn injury causes a T-helper-2 phenotype as demonstrated by depressed IL-2 and IFN-γ production and increased IL-5 production.

KW - Burn injury

KW - CD4

KW - CD8

KW - Cytotoxic T lymphocytes

KW - Effector limb

KW - Interferon-γ

KW - Interleukin- 5

KW - Interleukin-2

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