Rotavirus infection alters peripheral T-cell homeostasis in children with acute diarrhea.
The patterns of gene expression and the phenotypes of lymphocytes in peripheral blood mononuclear cells (PBMC) from children with diarrhea caused by rotavirus and healthy children were compared by using DNA microarray, quantitative PCR, and flow cytometry. We observed increased expression of a number of genes encoding proinflammatory cytokines and interferon or interferon-stimulated proteins and demonstrated activation of some genes involved in the differentiation, maturation, activation, and survival of B lymphocytes in PBMC of patients with rotavirus infection. In contrast, we observed a consistent pattern of lower mRNA levels for an array of genes involved in the various stages of T-cell development and demonstrated a reduction in total lymphocyte populations and in the proportions of CD4 and CD8 T lymphocytes from PBMC of patients. This decreased frequency of T lymphocytes was transient, since the proportions of T lymphocytes recovered to almost normal levels in convalescent-phase PBMC from most patients. Finally, rotavirus infection induced the activation and expression of the early activation markers CD83 and CD69 on a fraction of CD19 B cells and the remaining CD4 and CD8 T lymphocytes in acute-phase PBMC of patients; the expression of CD83 continued to be elevated and was predominantly exhibited on CD4 T lymphocytes in convalescent-phase PBMC. On the basis of these findings at the molecular, phenotypic, and physiologic levels in acute-phase PBMC, we conclude that rotavirus infection induces robust proinflammatory and antiviral responses and B-cell activation but alters peripheral T-cell homeostasis in children.
Wang
Yuhuan
Y
Division of Viral Diseases, Scientific Resources Program, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Dennehy
Penelope H
PH
Keyserling
Harry L
HL
Tang
Kevin
K
Gentsch
Jon R
JR
Glass
Roger I
RI
Jiang
Baoming
B
D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D016516:CD4-CD8 Ratio; D002675:Child, Preschool; D003967:Diarrhea / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006706:Homeostasis; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007223:Infant; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012400:Rotavirus Infections / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D000097802:CD83 Antigen; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007136:Immunoglobulins; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D000097802:CD83 Antigen; D000099192:CD69 Antigens