title: Functional comparison of T cells recognizing cytomegalovirus pp65 and intermediate-early antigen polypeptides in hematopoietic stem-cell transplant and solid organ transplant recipients.
abstract: The functional status of cytotoxic T lymphocyte (CTL) populations recognizing cytomegalovirus intermediate-early antigen (IE1) and pp65 polypeptides was investigated in peripheral blood mononuclear cells from hematopoietic stem-cell transplant (HSCT) and solid organ transplant recipients. Combined flow-based CD107a/b degranulation/mobilization and intracellular cytokine (ICC) assays using peptide libraries as antigens indicated that a significantly higher proportion of pp65-specific CTLs were in a more mature functional state, compared with IE1-specific CTLs. Degranulation/multiple cytokine ICC assays also indicated that a significantly higher proportion of pp65-specific than IE1-specific CTLs secreted both interferon- gamma and tumor necrosis factor- alpha and possessed greater cytotoxic potential. These results support our earlier findings of functional differences between CTLs recognizing individual epitopes within the IE1 and pp65 antigens in healthy donors and HSCT recipients and extend them to a broader array of human leukocyte antigen-restricted responses to those antigens. We also provide evidence of a relationship between cytotoxic function and the ability of cytomegalovirus-specific CTLs to secrete multiple cytokines.
authors.affiliation: Laboratory of Vaccine Research, Division of Information Sciences, Beckman Research Institute of the City of Hope, City of Hope Comprehensive Cancer Center, Duarte, CA 91010-3000, USA. slacey@coh.org
authors.forename: Simon F
authors.initials: SF
authors.lastname: Lacey
authors.forename: Corinna
authors.initials: C
authors.lastname: La Rosa
authors.forename: Wendy
authors.initials: W
authors.lastname: Zhou
authors.forename: Madeva C
authors.initials: MC
authors.lastname: Sharma
authors.forename: Joy
authors.initials: J
authors.lastname: Martinez
authors.forename: Aparna
authors.initials: A
authors.lastname: Krishnan
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Gallez-Hawkins
authors.forename: Lia
authors.initials: L
authors.lastname: Thao
authors.forename: Jeff
authors.initials: J
authors.lastname: Longmate
authors.forename: Ricardo
authors.initials: R
authors.lastname: Spielberger
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: Ajit
authors.initials: A
authors.lastname: Limaye
authors.forename: John A
authors.initials: JA
authors.lastname: Zaia
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D015550:Cell Degranulation; D016207:Cytokines / Q000096:biosynthesis; D003587:Cytomegalovirus / Q000276:immunology*; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000032:analysis; D052119:Lysosomal-Associated Membrane Protein 2 / Q000032:analysis; D008875:Middle Aged; D016377:Organ Transplantation; D010750:Phosphoproteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D052118:Lysosomal-Associated Membrane Protein 1; D052119:Lysosomal-Associated Membrane Protein 2; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C065418:cytomegalovirus matrix protein 65kDa