Dysregulated T helper type 1 (Th1) and Th17 responses in elderly hospitalised patients with infection and sepsis

OBJECTIVE: The role of Th1 and Th17 lymphocyte responses in human infection and sepsis of elderly patients has yet to be clarified. DESIGN: A prospective observational study of patients with sepsis, infection only and healthy controls. SETTING: The acute medical wards and intensive care units in a 1000 bed university hospital. PATIENTS: 32 patients with sepsis, 20 patients with infection, and 20 healthy controls. Patients and controls were older than 65 years of age. Patients with recognised underlying immune compromise were excluded. METHODS: Phenotype, differentiation status and cytokine production by T lymphocytes were determined by flow cytometry. MEASUREMENTS: The differentiation states of circulating CD3(+), CD4(+), and CD8(+) T cells were characterised as naive (CD45RA(+), CD197(+)), central memory (CD45RA(-), CD197(+)), effector memory (CD45RA(-), CD197(-)), or terminally differentated (CD45RA(+), CD197(-)). Expression of IL-12 and IL-23 receptors, and the transcription factors T-bet and RORγt, was analysed in circulating T lymphocytes. Expression of interferon- γ and IL-17A were analysed following stimulation in vitro. RESULTS: CD4(+) T cells from patients with infection predominantly expressed effector-memory or terminally differentiated phenotypes but CD4(+) T cells from patients with severe sepsis predominantly expressed naive phenotypes (p<0.0001). CD4(+) T cells expressing IL-23 receptor were lower in patients with sepsis compared to patients with infection alone (p = 0.007). RORγt expression by CD4(+) T cells was less frequent in patients with sepsis (p<0.001), whereas T-bet expressing CD8(+) T cells that do not express RORγt was lower in the sepsis patients. HLA-DR expression by monocytes was lower in patients with sepsis. In septic patients fewer monocytes expressed IL-23. CONCLUSION: Persistent failure of T cell activation was observed in patients with sepsis. Sepsis was associated with attenuated CD8(+)Th1 and CD4(+)Th17 based lymphocyte response.