Clinical significance of cytomegalovirus-specific T helper responses and cytokine production in lung transplant recipients.
Cytomegalovirus (CMV) disease continues to be a major problem for lung transplant recipients. In CMV-seropositive individuals, we detected two types of CMV-specific responses: a self-restricted response stimulated by soluble CMV antigen (sCMV-Ag) and a non-self-restricted response induced by CMV-infected cells (cCMV-Ag). Lung transplant recipients who develop the CMV-specific self-restricted T helper response have a low risk of recurrent CMV disease. In contrast, during CMV disease, lung transplant recipients exhibit only the non-self-restricted T helper responses. We characterized the T cell activation and the kinetics of cytokine production of sorted CD4+ and CD8+ T cells from PBLs of CMV seropositive donors. The two types of CMV antigens induced cytokine production in both T cell subsets. We also performed competitive RT-PCR for Granzyme B (GB) in BAL cells of lung transplant recipients prior to, during and following CMV disease. CMV disease was associated with increase in GB gene expression when was accompanied by acute cellular rejection while it remained low in patients with CMV disease that did not have a complicated course. In summary, CMV-activated T cells within the allograft may produce inflammatory cytokines and effector molecules that may promote allograft rejection.
Zeevi
A
A
Division of Transplantation Pathology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa., USA. zeevi+@pitt.edu
Spichty
K
K
Banas
R
R
Cai
J
J
Donnenberg
V S
VS
Donnenberg
A D
AD
Ahmed
M
M
Dauber
J
J
Iacono
A
A
Keenan
R
R
Griffith
B
B
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D053804:Granzymes; D006801:Humans; D007156:Immunologic Memory; D037181:Lectins, C-Type; D016040:Lung Transplantation / Q000009:adverse effects*; D008213:Lymphocyte Activation; D011183:Postoperative Complications / Q000276:immunology / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D016207:Cytokines; D053804:Granzymes; D037181:Lectins, C-Type; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D012697:Serine Endopeptidases; D000099192:CD69 Antigens; C509213:GZMB protein, human