Cytomegalovirus (CMV) is a widespread infection affecting 50-90% of the human population. A typical silent primary infection is followed by life-long persistence in the host under control by virus-specific CD8 (“killer”) and CD4 (“helper”) T cells. Although harmless in most people, CMV may cause disease and sequelae in patients with deficient cellular immunity, such as AIDS patients, recipients of organ transplants and children who have acquired the virus before birth. In this thesis we have characterized the cellular immunity to CMV in immunocompetent subjects, in patients receiving transplants and in infants.
In healthy individuals with latent CMV, the frequencies of CMV-specific CD8 T cells varied considerably between the donors. Within the same individual, the changes over time were usually small. In patients with primary, symptomatic CMV infection, the frequencies of CMV-specific CD8 T cells peaked within the first month after the appearance of symptoms. The frequencies then declined to levels similar to those in latently infected CMV carriers. The CD4 T-cell function followed the same pattern, but with lower peak values.Immunosuppressed renal transplant patients with latent CMV had CMV-specific CD4 cell function similar to healthy controls…
Contents
INTRODUCTION
The immune system
Adaptive immunity: Humoral and cellular immune responses
Immunity in fetuses and newborns
Cytomegalovirus
Structure and replication
Epidemiology
Clinical manifestations
CMV-specific immunological responses
Humoral immunity
Cellular immunity
CMV immunity in immunosuppressed patients
Immune evasion
AIMS OF THE STUDY
General aim
Specific aims
Paper I
Paper II
Paper III
Paper IV
STUDY DESIGN and METHODS
Ethics
Study groups: Inclusion, patient characteristics, and blood sampling
Healthy blood donors (Papers I, II, III)
Patients with primary CMV disease (Papers I and IV)
Kidney transplantation patients (Papers II and III)
Children (Paper IV)
CMV MHC I tetramers
CMV-specific T-cell activation and intracellular cytokine staining
Absolute counting of lymphocyte subsets
Cell counter (Paper IV)
Flow-Count beads (Papers I and III)
Flow cytometry
Statistics
RESULTS and DISCUSSION
Frequencies of CMV-specific (tetramer-binding) CD8 T cells
Healthy subjects with latent CMV infection
Healthy subjects with primary CMV infection
Immunosuppressed subjects
Infants and children
CD4 and CD8 T-cell function
Infants and adults with primary CMV infection
Latent CMV infection in immunosuppressed patients and healthy blood donors
Relation between frequency and function of CMV-specific cells
Immunodominance (Paper I)
General discussion
T cell dynamics in primary and latent CMV infection
Monitoring of CMV-specific immunity
CONCLUSIONS
Paper I
Paper II
Paper III
Paper IV
REFLECTIONS
FUTURE PERSPECTIVES
ACKNOWLEDGMENT
REFERENCES
Author: Lidehall, Anna Karin
Source: Uppsala University Library
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