Harms and benefits of lymphocyte subpopulations in patients with acute stroke

• Published in: Neuroscience Vol. 158; no. 3; pp. 1174 - 1183
• Main Authors: Urra, X, Cervera, Á, Villamor, N, Planas, A.M, Chamorro, Á
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 06.02.2009; Elsevier
• Subjects: Acute Disease; Aged; Aged, 80 and over; Antibody Formation - immunology; Apoptosis - immunology; Biological and medical sciences; Biomarkers - analysis; Cytokines - analysis; Cytokines - metabolism; Female; Fundamental and applied biological sciences. Psychology; Humans; Hydrocortisone - analysis; Hydrocortisone - blood; Immune Tolerance - immunology; Immunocompromised Host - immunology; Lymphocyte Count; lymphocytes; Lymphocytes - cytology; Lymphocytes - immunology; Lymphopenia - diagnosis; Lymphopenia - immunology; Lymphopenia - physiopathology; Male; Medical sciences; Middle Aged; Neurology; outcome; Predictive Value of Tests; Prospective Studies; Stress, Physiological - immunology; stroke; Stroke - complications; Stroke - immunology; Stroke - physiopathology; stroke-associated infection; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; magnetic resonance imaging; MRI; rtPA; cluster of differentiation; TNF; phorbol myristate acetate; MESF; IFN; modified Rankin Scale; natural killer; Th; stroke-associated infection; metanephrine; helper T; CSF; DWI; National Institutes of Health Stroke Scale; interleukin; outcome; NIHSS; recombinant tissue plasminogen activator; CD; MN; lymphocytes; IL; regulatory T; PMA; Treg; interferon; stroke; molecules of equivalent soluble fluorochrome; mRS; APC; cytotoxic T lymphocyte; tumor necrosis factor; diffusion-weighted imaging; cerebrospinal fluid; antigen presenting cell; CTL; SAI; NK; Human; Nervous system diseases; Stroke; Acute; Cardiovascular disease; Cerebral disorder; Vascular disease; Infection; Central nervous system disease; Lymphocyte; Cerebrovascular disease
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.06.014

Abstract Lymphocytes are major players in the development of innate and adaptive immune responses but their behavior in patients with acute stroke has received little attention. Experimental procedures: Using flow cytometry we identified total lymphocytes, T cells, helper T (Th) cells, cytotoxic T lymphocytes (CTL), natural killer (NK) cells, B cells, and regulatory T (Treg) cells in 46 consecutive patients with acute stroke within a median of 180 min of clinical onset, and at days 2, 7, and 90. Daily neurological score (National Institutes of Health Stroke Scale), diffusion-weighted imaging on brain magnetic resonance imaging, functional impairment, and stroke-associated infection (SAI) at day 7 were assessed. Apoptosis in lymphocyte subsets, tumor necrosis factor (TNF) -α/interleukin (IL) -4 production in stimulated Th and CTL, cluster of differentiation 86 (CD86) (B7-2) expression in B cells, cortisol and metanephrine in serum were measured. Multivariate analyses were used to evaluate SAI, and stroke outcome. Results: Increased apoptosis and a fall of T, Th, CTL, B, and Treg cells were observed after stroke. Severer stroke on admission and SAI disclosed a greater decline of T, Th, and CTL cells. Increased cortisol and metanephrine was associated with severe stroke and SAI, and inversely correlated with T, and CTL. T cells, and CTL were correlated with infarct growth. Stroke but not SAI resulted in lower TNF-α production in Th cells. SAI showed the greatest fall of lymphocytes, T, Th, and CTL, but not B cells, or Treg. Poor outcome was associated with reduced levels of B cells, and increased expression of CD86 in B cells, but not with SAI. Conclusion: Lymphopenia and increased apoptosis of T, Th, CTL, Treg and B cells are early signatures after human stroke. A decreased cellular response after stroke is a marker of ongoing brain damage, the stress response, and a higher risk of infection. A lower humoral response is predictor of poorer long-term outcome.