Differential mobilization of functionally distinct natural killer subsets during acute psychologic stress.

OBJECTIVE AND METHODS Two functionally distinct natural killer (NK) subsets can be identified according to surface CD56 expression: CD56lo cells compose the majority of NK cells and function as cytotoxic cells, whereas CD56hi cells have an immunomodulatory function through the secretion of cytokines. These NK subsets also differ in the expression levels of adhesion molecules such as CD62L and CD11a, indicating distinct potentials to migrate to lymphoid and nonlymphoid tissues. We investigated whether NK cell mobilization during acute stress varies according to these functional and phenotypic distinctions. METHODS AND RESULTS Fifty-three undergraduate students performed a public-speaking task and 21 students participated in a control session. The task increased heart rate and catecholamines. No change was observed for the immunoregulatory CD56hi NK subset, whereas the number of cytotoxic CD56lo NK cells tripled. In line with the observation that NK mobilization is related to cytotoxic function, we found larger increases in NK cells that express higher levels of CD16 (a receptor that mediates antibody-dependent cytotoxicity). Consistent with known subset differences in adhesion molecule expression, we also found larger stress-induced increases for NK cells that were CD62L-negative and CD11ahi. Plasma levels of soluble CD62L remained unaltered, suggesting that the increase in CD62L-negative NK cells did not result from CD62L shedding. Regression analyses demonstrated independent contributions of epinephrine and norepinephrine to NK subset mobilization. CONCLUSION The marked specificity and robustness of these effects support the idea that NK cell mobilization is a functionally relevant response that is aimed at protecting the organism during acutely stressful situations.