title: Clinical significance of CMV-specific T helper responses in lung transplant recipients.
abstract: BACKGROUND
  Cytomegalovirus (CMV) disease continues to be a major problem for lung transplant patients who generate an inefficient immune response to control this viral infection. Both T helper and cytotoxic T cells are thought to play an important role in prevention and control of CMV disease. We investigated the clinical significance of CMV-specific memory responses in lung transplant recipients.
  
  
  METHODS
  Peripheral blood samples (140) were collected from 99 lung transplant recipients. Patients were grouped according to their pre-transplant CMV serological status as recipient/donor (R-/D+, 25 patients), 28 R+/D+ patients, 35 R+/D- patients and 11 R-/D- patients. Memory responses to CMV whole antigen, 5 CMV proteins, and tetanus toxoid (TT) were measured in a 6-day proliferative assay. Results were expressed as the stimulation index (SI = experimental cpm/background cpm), and were considered positive if the SI was >3 and the cpm values were over 1,000.
  
  
  RESULTS
  The frequency of positive CMV memory responses was similar in three groups: 64% for R-/D+, 63% for R+/D+ and 56% for R+/D- except for R-/D- (21%). The memory response to TT was similar for all four groups (70% of samples were positive). The level of responsiveness to individual CMV proteins was much higher in R+/D+ group (65%) than the other two groups (35% for R+/D-, and 31% for R-/D+). We determined the temporal relationship between the presence of CMV-specific memory responses and the diagnosis of CMV disease. In the R-/D+ group, 16 of 17 patients who had CMV disease eventually developed CMV-specific memory. In those patients (n = 3) who failed to develop CMV-specific T helper response for a prolonged time, all had recurrent CMV disease. In the R+/D+ group, 4 of 8 patients with CMV disease exhibited CMV-specific memory responses. Three of 4 patients in whom we observed a persistent absence of CMV-specific memory had multiple episodes of CMV pneumonitis. In the R+/D- group, only one of 4 patients with CMV disease had suppressed CMV-specific memory response after first episode of CMV pneumonitis and had recurrent disease.
  
  
  CONCLUSIONS
  In lung transplant recipients, the loss or persistent lack of CMV-specific memory following infection was associated with chronic CMV disease. These data suggest that monitoring T helper memory responses following primary CMV infection or after augmented immunosuppression for treatment of rejection may identify those patients at risk for morbidity associated with recurrent CMV disease.
authors.affiliation: Division of Transplantation Pathology, Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, PA 15261, USA. Zeevi+@pitt.edu
authors.forename: A
authors.initials: A
authors.lastname: Zeevi
authors.forename: P
authors.initials: P
authors.lastname: Morel
authors.forename: K
authors.initials: K
authors.lastname: Spichty
authors.forename: J
authors.initials: J
authors.lastname: Dauber
authors.forename: S
authors.initials: S
authors.lastname: Yousem
authors.forename: P
authors.initials: P
authors.lastname: Williams
authors.forename: W
authors.initials: W
authors.lastname: Grgurich
authors.forename: S
authors.initials: S
authors.lastname: Pham
authors.forename: A
authors.initials: A
authors.lastname: Iacono
authors.forename: R
authors.initials: R
authors.lastname: Keenan
authors.forename: R
authors.initials: R
authors.lastname: Duquesnoy
authors.forename: B
authors.initials: B
authors.lastname: Griffith
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007963:Leukocytes, Mononuclear; D016040:Lung Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D010750:Phosphoproteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D010750:Phosphoproteins; D013745:Tetanus Toxoid; D014764:Viral Proteins