title: Vitamin D Supplementation Modulates T Cell-Mediated Immunity in Humans: Results from a Randomized Control Trial.
abstract: BACKGROUND
  Although studies have linked vitamin D deficiency with immune-mediated diseases, data demonstrating a direct effect on T-cell function are sparse.
  
  
  OBJECTIVE
  Our objective was to determine whether oral vitamin D3 influences T-cell activation in humans with vitamin D deficiency.
  
  
  METHODS
  This was a single-center ancillary study within Vitamin D Therapy in Individuals at High Risk of Hypertension, a double-blind, multicenter, randomized controlled trial.
  
  
  METHODS
  This study was undertaken in a single academic medical center.
  
  
  METHODS
  Adults with vitamin D deficiency and untreated pre- or early stage I hypertension were included.
  
  
  METHODS
  In Vitamin D Therapy in Individuals at High Risk of Hypertension, participants were randomized to either low- (400 IU daily) or high- (4000 IU daily) dose oral vitamin D3 for 6 months. In this ancillary study of 38 patients, we measured CD4+ T-cell activation estimated by intracellular ATP release after stimulation of whole blood with plant lectin phytohemagglutinin collected at baseline (pretreatment) and 2-month follow-up.
  
  
  METHODS
  Determining whether ATP level changes were significantly different between treatment groups was the main outcome measure.
  
  
  RESULTS
  Treatment with 4000 IU of vitamin D3 decreased intracellular CD4+ ATP release by 95.5 ng/ml (interquartile range, -219.5 to 105.8). In contrast, 400 IU of vitamin D3 decreased intracellular CD4+ ATP release by 0.5 ng/ml (interquartile range, -69.2 to 148.5). In a proportional odds model, high-dose vitamin D3 was more likely than low-dose vitamin D3 to decrease CD4+ ATP release (odds ratio, 3.43; 95% confidence interval, 1.06-1.11).
  
  
  CONCLUSIONS
  In this ancillary study of a randomized controlled trial, we found that high-dose vitamin D3 significantly reduced CD4+ T-cell activation compared to low-dose vitamin D3, providing human evidence that vitamin D can influence cell-mediated immunity.
authors.affiliation: Division of Gastroenterology (G.G.K.), Scripps Clinic, La Jolla, California; Scripps Translational Science Institute (G.G.K.), La Jolla, California 92037; Division of Gastroenterology (G.G.K., M.R.B., A.T.C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Cardiology (P.A.), University of Alabama, Birmingham, Alabama 35210; Department of Biostatistics (Y.S., S.H., F.H., D.O., T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (C.N.-C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology (J.K.), Brigham and Women's Hospital, Boston, Massachusetts 02115; and Clinical and Translational Epidemiology Unit (A.T.C.), Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Gauree Gupta
authors.initials: GG
authors.lastname: Konijeti
authors.affiliation: Division of Gastroenterology (G.G.K.), Scripps Clinic, La Jolla, California; Scripps Translational Science Institute (G.G.K.), La Jolla, California 92037; Division of Gastroenterology (G.G.K., M.R.B., A.T.C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Cardiology (P.A.), University of Alabama, Birmingham, Alabama 35210; Department of Biostatistics (Y.S., S.H., F.H., D.O., T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (C.N.-C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology (J.K.), Brigham and Women's Hospital, Boston, Massachusetts 02115; and Clinical and Translational Epidemiology Unit (A.T.C.), Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Arora
authors.affiliation: Division of Gastroenterology (G.G.K.), Scripps Clinic, La Jolla, California; Scripps Translational Science Institute (G.G.K.), La Jolla, California 92037; Division of Gastroenterology (G.G.K., M.R.B., A.T.C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Cardiology (P.A.), University of Alabama, Birmingham, Alabama 35210; Department of Biostatistics (Y.S., S.H., F.H., D.O., T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (C.N.-C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology (J.K.), Brigham and Women's Hospital, Boston, Massachusetts 02115; and Clinical and Translational Epidemiology Unit (A.T.C.), Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Boylan
authors.affiliation: Division of Gastroenterology (G.G.K.), Scripps Clinic, La Jolla, California; Scripps Translational Science Institute (G.G.K.), La Jolla, California 92037; Division of Gastroenterology (G.G.K., M.R.B., A.T.C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Cardiology (P.A.), University of Alabama, Birmingham, Alabama 35210; Department of Biostatistics (Y.S., S.H., F.H., D.O., T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (C.N.-C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology (J.K.), Brigham and Women's Hospital, Boston, Massachusetts 02115; and Clinical and Translational Epidemiology Unit (A.T.C.), Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Song
authors.affiliation: Division of Gastroenterology (G.G.K.), Scripps Clinic, La Jolla, California; Scripps Translational Science Institute (G.G.K.), La Jolla, California 92037; Division of Gastroenterology (G.G.K., M.R.B., A.T.C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Cardiology (P.A.), University of Alabama, Birmingham, Alabama 35210; Department of Biostatistics (Y.S., S.H., F.H., D.O., T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (C.N.-C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology (J.K.), Brigham and Women's Hospital, Boston, Massachusetts 02115; and Clinical and Translational Epidemiology Unit (A.T.C.), Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Shi
authors.initials: S
authors.lastname: Huang
authors.affiliation: Division of Gastroenterology (G.G.K.), Scripps Clinic, La Jolla, California; Scripps Translational Science Institute (G.G.K.), La Jolla, California 92037; Division of Gastroenterology (G.G.K., M.R.B., A.T.C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Cardiology (P.A.), University of Alabama, Birmingham, Alabama 35210; Department of Biostatistics (Y.S., S.H., F.H., D.O., T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (C.N.-C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology (J.K.), Brigham and Women's Hospital, Boston, Massachusetts 02115; and Clinical and Translational Epidemiology Unit (A.T.C.), Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Frank
authors.initials: F
authors.lastname: Harrell
authors.affiliation: Division of Gastroenterology (G.G.K.), Scripps Clinic, La Jolla, California; Scripps Translational Science Institute (G.G.K.), La Jolla, California 92037; Division of Gastroenterology (G.G.K., M.R.B., A.T.C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Cardiology (P.A.), University of Alabama, Birmingham, Alabama 35210; Department of Biostatistics (Y.S., S.H., F.H., D.O., T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (C.N.-C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology (J.K.), Brigham and Women's Hospital, Boston, Massachusetts 02115; and Clinical and Translational Epidemiology Unit (A.T.C.), Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.affiliation: Division of Gastroenterology (G.G.K.), Scripps Clinic, La Jolla, California; Scripps Translational Science Institute (G.G.K.), La Jolla, California 92037; Division of Gastroenterology (G.G.K., M.R.B., A.T.C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Cardiology (P.A.), University of Alabama, Birmingham, Alabama 35210; Department of Biostatistics (Y.S., S.H., F.H., D.O., T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (C.N.-C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology (J.K.), Brigham and Women's Hospital, Boston, Massachusetts 02115; and Clinical and Translational Epidemiology Unit (A.T.C.), Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Dillon
authors.initials: D
authors.lastname: O'Neill
authors.affiliation: Division of Gastroenterology (G.G.K.), Scripps Clinic, La Jolla, California; Scripps Translational Science Institute (G.G.K.), La Jolla, California 92037; Division of Gastroenterology (G.G.K., M.R.B., A.T.C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Cardiology (P.A.), University of Alabama, Birmingham, Alabama 35210; Department of Biostatistics (Y.S., S.H., F.H., D.O., T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (C.N.-C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology (J.K.), Brigham and Women's Hospital, Boston, Massachusetts 02115; and Clinical and Translational Epidemiology Unit (A.T.C.), Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Joshua
authors.initials: J
authors.lastname: Korzenik
authors.affiliation: Division of Gastroenterology (G.G.K.), Scripps Clinic, La Jolla, California; Scripps Translational Science Institute (G.G.K.), La Jolla, California 92037; Division of Gastroenterology (G.G.K., M.R.B., A.T.C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Cardiology (P.A.), University of Alabama, Birmingham, Alabama 35210; Department of Biostatistics (Y.S., S.H., F.H., D.O., T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (C.N.-C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology (J.K.), Brigham and Women's Hospital, Boston, Massachusetts 02115; and Clinical and Translational Epidemiology Unit (A.T.C.), Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.affiliation: Division of Gastroenterology (G.G.K.), Scripps Clinic, La Jolla, California; Scripps Translational Science Institute (G.G.K.), La Jolla, California 92037; Division of Gastroenterology (G.G.K., M.R.B., A.T.C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Cardiology (P.A.), University of Alabama, Birmingham, Alabama 35210; Department of Biostatistics (Y.S., S.H., F.H., D.O., T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (T.J.W.), Vanderbilt University, Nashville, Tennessee 37232; Division of Cardiology (C.N.-C.), Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology (J.K.), Brigham and Women's Hospital, Boston, Massachusetts 02115; and Clinical and Translational Epidemiology Unit (A.T.C.), Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D002762:Cholecalciferol / Q000097:blood / Q000627:therapeutic use*; D015331:Cohort Studies; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014808:Vitamin D Deficiency / Q000097:blood; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D014815:Vitamins; D002762:Cholecalciferol; D000255:Adenosine Triphosphate