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Regulatory T cells are persistently enriched in the peripheral blood of head-injury patients

Introduction

We have previously shown that a significant proportion of patients have increased numbers of lymphocytes proliferating in response to myelin basic protein 10 days post traumatic brain injury (TBI); associated with a trend for more favourable outcome [1]. This suggests that the adaptive immune response may have a protective role following TBI, as demonstrated in animal models [2]. In this study, we further explored this process by examining the effect of TBI on regulatory T cell (Treg) numbers, and determining whether a change in Treg frequency was long lived.

Methods

We recruited 12 patients with severe or moderate TBI who required protocol-driven therapy to maintain cerebral perfusion and intracranial pressure. Blood samples were taken within 72 hours and 10 days post TBI. A separate group of patients was studied 6 months post TBI. Age-matched and sex-matched healthy volunteers were used as controls. Peripheral blood mononuclear cells (PBMCs) were isolated. Flow cytometry was used to identify Tregs according to the surface expression of markers (CD4/CD25high/CD45ROhigh/CD127low).

Results

When compared with controls, patients at 10 days and at 6 months post TBI showed a greater proportion of PBMCs with a Treg phenotype (Mann–Whitney U test; P < 0.01 and P < 0.05, respectively). The proportion of Treg cells at 72 hours was higher than controls, but this difference did not reach significance. See Figure 1.

Figure 1
figure1

Treg frequency post TBI.

Conclusion

We have shown that TBI upregulates CD4+ T cells with a regulatory phenotype. This effect is sustained for at least 6 months, and may modulate protective autoimmunity. Better understanding of the functional capacity and specificity of lymphocytes identified as Tregs may provide therapeutic targets.

References

  1. 1.

    Cox AL, et al.: J Neuroimmunol. 2006, 174: 180-186. 10.1016/j.jneuroim.2006.01.007

  2. 2.

    Hauben E, et al.: Lancet. 2000, 354: 286-287. 10.1016/S0140-6736(99)05140-5

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Galtrey, E., Cox, A., Chatfield, D. et al. Regulatory T cells are persistently enriched in the peripheral blood of head-injury patients. Crit Care 13, P82 (2009). https://doi.org/10.1186/cc7246

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Keywords

  • Traumatic Brain Injury
  • Peripheral Blood Mononuclear Cell
  • Protective Role
  • Intracranial Pressure
  • Treg Cell