Phenotypic and functional characterization of CD8(+) T cell clones specific for a mouse cytomegalovirus epitope.
A series of CD8(+) T cell clones, specific for the IE1 epitope YPHFMPTNL, of the immediate-early protein 1 of the murine cytomegalovirus (MCMV) were generated in order to determine their protective activity against this infection and correlate their phenotypic markers with antiviral activity. We found that the adoptive transfer of three of these anti-MCMV CD8(+) T cell clones into irradiated naive mice resulted in protection against challenge, while another CD8(+) T cell clone, of the same specificity, failed to confer protection. The clones that conferred protection against lethal challenge reduced greatly viral replication in the lung and other organs of the mice. Using one of the protective anti-MCMV CD8(+) T cell clones we found that in order to be fully protective the cells had to be transferred to recipient mice no later than 1 day after MCMV challenge. The adoptive transfer of these CD8(+) T cell clones also protected CD4(+) T-cell-depleted mice. Phenotypic characterization of the anti-MCMV clones revealed that the nonprotective clone expressed very low levels of CD8 molecules and produced only small amounts of TNF-alpha upon antigenic stimulation. Most importantly, our current study demonstrates that this MHC class I-restricted IE1 epitope of MCMV is efficiently presented to CD8(+) T cell clones in vivo and further strengthens the possibility of the potential use of CD8(+) T cell clones as immunotherapeutic tools against cytomegalovirus-induced disease.
Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York 10010, USA.
J A
JA
Fernandez
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F
Zavala
M
M
Tsuji
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006566:Herpesviridae Infections / Q000517:prevention & control*; D017874:Immediate-Early Proteins / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology*; D010641:Phenotype; D013997:Time Factors; D014764:Viral Proteins
D018984:Epitopes, T-Lymphocyte; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D016056:Immunodominant Epitopes; D014764:Viral Proteins