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Differential Mobilization of Functionally Distinct Natural Killer Subsets During Acute Psychologic Stress

From the College of Dentistry, University of Illinois at Chicago, Chicago, Illionis (J.A.B., P.T.M.); the School of Dentistry (J.A.B.) and the Department of Psychology (G.G.B.), The Ohio State University, Columbus, Ohio; and the Department of Psychology, University of Chicago, Chicago, Illinois (J.T.C.).

Address correspondence and reprint requests to Phillip T. Marucha, DMD, PhD, The University of Illinois at Chicago, College of Dentistry, Department of Periodontics (MC 859), 801 S. Paulina St., Chicago, IL 60611. E-mail marucha{at}uic.edu

Objective and Methods: Two functionally distinct natural killer (NK) subsets can be identified according to surface CD56 expression: CD56^lo cells compose the majority of NK cells and function as cytotoxic cells, whereas CD56^hi 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 CD56^hi NK subset, whereas the number of cytotoxic CD56^lo 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 CD11a^hi. 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.

Key Words: immunosurveillance • innate immunity • social stress • laboratory stress • L-selectin

Abbreviations: ANOVA = analysis of variance; CD = cluster of differentiation; ECG = electrocardiogram; ELISA = enzyme-linked immunosorbent assay; Hb = hemoglobin; HPLC = high-pressure liquid chromatography; Htc = hematocrit; NK = natural killer; POMS = Profile of Mood States; sCD62L = soluble CD62L; SEM = standard error of mean.

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