CD8+ T cells express a T-helper 1–like phenotype after burn injury

doi:10.1067/msy.2001.115835

Surgery

Volume 130, Issue 2, August 2001, Pages 210-216

Presented at the 62nd Annual Meeting of the Society of University Surgeons, Chicago, Ill, February 8-10, 2001.

https://doi.org/10.1067/msy.2001.115835 Get rights and content

Abstract

Background. Previous studies suggest that CD8⁺ T cells are immunosuppressive after burn injury, but recent reports indicate that CD8⁺ T cells have several functions similar to CD4⁺ T cells, including the secretion of cytokines. This study uses HY male antigen in transgenic HY female mice to determine the antigen-specific response of activated CD8⁺ T cells after burn injury. Methods. HY TCR transgenic female mice underwent burn or sham injury. Seventy-two hours after the burn, splenocytes were stimulated with 20 μmol/L HY peptide for 16, 48, and 64 hours; cellular proliferation, intracellular interferon-γ and interleukin-2, and apoptosis were measured. Results. Burn injury significantly impaired proliferation to HY antigen (P ≤.05). Activated CD8⁺ T cells from burned mice showed increased intracellular interferon-γ and interleukin-2 16 hours after stimulation compared with sham (P ≤.05) and at no time was less than control mice. The percent of CD8⁺ T cells decreased with the time of stimulation but was not due to apoptosis by Annexin V staining. Conclusions. Activated CD8⁺ T cells express a T_H1-like phenotype after burn injury. This provides evidence that CD8⁺ T cells are not simply suppressive and that is consistent with data that CD4⁺ T cells are primed for a T_H1 response after burn injury. (Surgery 2001;130:210-6.)

Section snippets

Animals

C57BL/6 (H-2^b)-transgenic mice (HY TCR)¹⁶ that carry the transgene specific for male HY antigen were obtained from the National Institute of Arthritis and Infectious Diseases through Taconic Laboratories (Germantown, NY).

Mouse burn injury

Fifteen-to 20-gm, 6-week-old, female HY TCR C57BL/6 mice were used as subjects in all experiments. All protocols were performed in accordance with the National Institutes of Health guidelines and approved by the University of North Carolina Committee on Animal Research. The

Effect of burn injury antigen-specific proliferation in HY TCR mice

To ensure that we had a measurable immunologic deficit in T-cell activity after burn injury, we chose 72 hours after the burn injury to kill the mice and to perform our antigen-specific stimulation experiments. In our previous studies, CTL activity is maximally depressed 72 hours after a 20% burn,18, 19 and we expected that the HY antigen–specific proliferative response in the HY TCR transgenic mouse model would be suppressed at this time point as well. For nearly all concentrations of HY

Discussion

In this study, we demonstrate that a 20% TBSA burn induces an antigen-specific, dysfunctional T-cell proliferative response 72 hours after injury in HY TCR transgenic mice. This immune dysfunction is associated with a T_H1-like phenotype in activated CD8⁺ T cells from burned mice, with increased IFN-γ and IL-2 intracellular staining, compared with control mice. Furthermore, this T_H1-like phenotype is sustained after prolonged antigen-specific stimulation in culture. Although the percentage of CD8

References (26)

TR Mosmann et al.
The expanding universe of T-cell subsets: Th1, Th2 and more [see comments]
Immunol Today
(1996)
D Decker et al.
Surgical stress induces a shift in the type-1/type-2 T-helper cell balance, suggesting down-regulation of cell-mediated and up-regulation of antibody-mediated immunity commensurate to the trauma
Surgery
(1996)
E Lin et al.
Inflammatory cytokines and cell response in surgery
Surgery
(2000)
TR Mosmann et al.
Functions of CD8 T-cell subsets secreting different cytokine patterns
Semin Immunol
(1997)
EG Kavanagh et al.
Burn injury primes naive CD4+ T cells for an augmented T-helper 1 response
Surgery
(1998)
MR Kell et al.
A central role for CD95 (Fas) in T-cell reactivity after injury
Surgery
(2000)
CS Hultman et al.
Early, complete burn wound excision partially restores cytotoxic T lymphocyte function
Surgery
(1995)
JP Hunt et al.
The effector component of the cytotoxic T-lymphocyte response has a biphasic pattern after burn injury
J Surg Res
(1998)
S Roy et al.
Morphine synergizes with lipopolysaccharide in a chronic endotoxemia model
J Neuroimmunol
(1999)
AK De et al.
Induction of global anergy rather than inhibitory Th2 lymphokines mediates posttrauma T cell immunodepression
Clin Immunol
(2000)

EL Reinherz et al.

Current concepts in immunology: regulation of the immune response-inducer and suppressor T-lymphocyte subsets in human beings

N Engl J Med

(1980)

CL Miller et al.

Changes in lymphocyte activity after thermal injury: the role of suppressor cells

J Clin Invest

(1979)

DB Gough et al.

Suppressor T-cell levels are unreliable indicators of the impaired immune response following thermal injury

J Trauma

(1992)

Cited by (14)

Sex differences and estrogen modulation of the cellular immune response after injury
2008, Cellular Immunology
Citation Excerpt :
Consistent with this paradigm, some studies demonstrate a Th2 (Tc2) phenotype cytokine secretion by CD8+ T cells with a decreased antigen-specific proliferative and cytolytic response [77,78]. However, other groups have evidence of CD8+ T cells producing Th1 (Tc1) cytokines similar to their CD4+ T cell counterparts following burn [79]. To add confusion to the story, other laboratories suggest it is CD4+ CD25+ T regulatory cells that are the main players in down-regulating the aberrant inflammatory response following burn [80].
Cell-mediated immunity is extremely important for resolution of infection and for proper healing from injury. However, the cellular immune response is dysregulated following injuries such as burn and hemorrhage. Sex hormones are known to regulate immunity, and a well-documented dichotomy exists in the immune response to injury between the sexes. This disparity is caused by differences in immune cell activation, infiltration, and cytokine production during and after injury. Estrogen and testosterone can positively or negatively regulate the cellular immune response either by aiding in resolution or by compounding the morbidity and mortality. It is apparent that the hormonal dysregulation is dependent not only on the type of injury sustained but also the amount of circulating hormones. Therefore, it may be possible to design sex-specific therapies to improve immunological function and patient outcome.
Transgenic and gene knock-out techniques and burn research
2005, Journal of Surgical Research
The development of transgenic technology has given researchers a powerful tool to examine biological effects, and the response to injury is no exception. Techniques such as pronuclear injection, targeted homologous recombination, and Cre/loxP gene excision are being used to construct animals with specific genetic designs; these are exploited to learn the role of genes in the response to severe burn. We review the construction of transgenic animals, pitfalls and benefits of this relatively new technique, and how this technique has been used in burn research.
DATING DRY BURN INJURY IN HUMAN PATIENTS BY FLOW CYTOMETRY OF CD4+ AND CD8+ T-CELLS IN THE BLOOD
2021, The Egyptian Journal of Forensic Sciences and Applied Toxicology
Xenogeneic mesenchymal stromal cells improve wound healing and modulate the immune response in an extensive burn model
2016, Cell Transplantation
Flagellin treatment prevents increased susceptibility to systemic bacterial infection after injury by inhibiting anti-inflammatory IL-10+ IL-12- neutrophil polarization
2014, PLoS ONE
Radiation combined with thermal injury induces immature myeloid cells
2012, Shock

View all citing articles on Scopus

^*: Supported in part by National Institutes of Health grants AI20288, AI41580 and the North Carolina Jaycee Burn Center.

^**: Reprint requests: Bruce A. Cairns, MD, Department of Surgery, CB# 7210, 165 Burnett-Womack Bldg, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7210.

View full text

Society of University SurgeonsCD8+ T cells express a T-helper 1–like phenotype after burn injury*,**

Abstract

Section snippets

Animals

Mouse burn injury

Effect of burn injury antigen-specific proliferation in HY TCR mice

Discussion

Immunol Today

Surgery

Surgery

Semin Immunol

Surgery

Surgery

Surgery

J Surg Res

J Neuroimmunol

Clin Immunol

Current concepts in immunology: regulation of the immune response-inducer and suppressor T-lymphocyte subsets in human beings

N Engl J Med

Changes in lymphocyte activity after thermal injury: the role of suppressor cells

J Clin Invest

Suppressor T-cell levels are unreliable indicators of the impaired immune response following thermal injury

J Trauma

Society of University Surgeons
CD8⁺ T cells express a T-helper 1–like phenotype after burn injury*,**