Functional comparison of T cells recognizing cytomegalovirus pp65 and intermediate-early antigen polypeptides in hematopoietic stem-cell transplant and solid organ transplant recipients.
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.
Lacey
Simon F
SF
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
La Rosa
Corinna
C
Zhou
Wendy
W
Sharma
Madeva C
MC
Martinez
Joy
J
Krishnan
Aparna
A
Gallez-Hawkins
Ghislaine
G
Thao
Lia
L
Longmate
Jeff
J
Spielberger
Ricardo
R
Forman
Stephen J
SJ
Limaye
Ajit
A
Zaia
John A
JA
Diamond
Don J
DJ
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*
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