CD4 and neoplasm: It is also important to appreciate that stress caused by models not specific to HPA or SNS signalling, such as the chronic restraint of mice, leads to an increase in tumour growth driven by a significant reduction in circulating CD4+ T cells, a decrease in the production of the key Th1 cytokines IFN-γ and TNF-α, and the impairment of direct lymphocyte cytotoxicity (Frick 2009).