Table 2.

Possible mechanisms underlying the stimulatory effects of repeated cold stress on cell-mediated immunity

	CTLs and other cytotoxic immune cells	NK cells*
Expansion/peripheral recruitment	brief action** of the SNS [39-41] (via norepinephrine) on β2-adrenergic receptors of CD8+ T lymphocytes [36-38]; elevated plasma levels of ACTH [88,89], T4 [90], and beta-endorphin [91];	brief action** of the SNS (via norepinephrine) on β2-adrenergic receptors of NK cells [37,42,44]; upregulation of beta-endorphin [92], IL-2 [93], T3 [94] and T4 [95];
Activation	brief action** of the SNS (via norepinephrine) [36,39,96-98], beta-endorphin [91,99-101], T3 [102], or T4 [90,103,104] or sustained action of ACTH [88]; increased phagocytic index [43], downregulation of testosterone [105-107] or α1-antitrypsin [108];	-
Cytolytic activity	upregulation of ACTH [88,89], beta-endorphin [109,110], IL-2 [111-113], IL-6 [114,115], TNF-α [116-118], combination of IL-2 + IL-6 [119,120], or IL-2 + TNF-α [121]; downregulation of α1-antitrypsin [122,123];	elevated plasma levels of IL-2 [93], beta-endorphin [124-126], ACTH [127,128], T3 [129,130] or T4 [131,132];

* Continuous hypothermia [133] (lowered core body temperature which cannot normally result from a brief exposure to cold in most mammals [52,53]) or continuous exposure to acute cold (4 hours or longer [134]) have been shown to reduce both the number and activity of peripheral NK cells.

** Continuous elevated levels of norepinephrine or other β2-adrenergic agonists (3 hours or longer) appear to have an opposite effect: reduction in peripheral CTLs and NK cells and inhibition of their activity [42,135,136].