Anti-IE1 CD4+ T-cell clones kill peptide-pulsed, but not human cytomegalovirus-infected, target cells.
Cellular immunity plays a major role in the control of human cytomegalovirus (HCMV) infection. CD4(+) T lymphocytes have been shown to contribute to this function but their precise role is a matter of debate. Although CD4(+) T cells have been shown to kill target cells through the perforin/granzyme pathway, whether HCMV-specific CD4(+) T cells are capable of killing HCMV-infected targets has not yet been documented. In the present paper, we have taken advantage of well established cellular reagents to address this issue. Human CD4(+) T-cell clones specific for the major immediate-early protein IE1 were shown to perform perforin-based cytotoxicity against peptide-pulsed targets. However, when tested on infected anitgen presenting cell targets, cytotoxicity was not detectable, although gamma interferon (IFN-gamma) production was significant. Furthermore, cytotoxicity against peptide-pulsed targets was inhibited by HCMV infection, whereas IFN-gamma production was not modified, suggesting that antigen processing was not altered. Remarkably, degranulation of CD4(+) T cells in the presence of infected targets was significant. Together, our data suggest that impaired cytotoxicity is not due to failure to recognize infected targets but rather to a mechanism specifically related to cytotoxicity.
Delmas
Sandra
S
INSERM U563, Centre de Physiopathologie de Toulouse Purpan, IFR 30, Centre Hospitalier Purpan, 31024 Toulouse Cedex, France.
Brousset
Pierre
P
INSERM U563, Centre de Physiopathologie de Toulouse Purpan, IFR 30, Centre Hospitalier Purpan, 31024 Toulouse Cedex, France.
Clément
Danièle
D
INSERM U563, Centre de Physiopathologie de Toulouse Purpan, IFR 30, Centre Hospitalier Purpan, 31024 Toulouse Cedex, France.
Le Roy
Emmanuelle
E
INSERM U563, Centre de Physiopathologie de Toulouse Purpan, IFR 30, Centre Hospitalier Purpan, 31024 Toulouse Cedex, France.
Davignon
Jean-Luc
JL
INSERM U563, Centre de Physiopathologie de Toulouse Purpan, IFR 30, Centre Hospitalier Purpan, 31024 Toulouse Cedex, France.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002999:Clone Cells; D003587:Cytomegalovirus / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000633:toxicity; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000633:toxicity; D014764:Viral Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014764:Viral Proteins; D054353:Perforin