CD59 blockade enhances antigen-specific CD4+ T cell responses in humans: a new target for cancer immunotherapy?
CD59, a broadly expressed GPI-anchored molecule, regulates formation of the membrane attack complex of the complement cascade. We previously demonstrated that mouse CD59 also down-modulates CD4(+) T cell activity in vivo. In this study, we explored the role of CD59 on human CD4(+) T cells. Our data demonstrate that CD59 is up-regulated on activated CD4(+) T cells and serves to down-modulate their activity in response to polyclonal and Ag-specific stimulation. The therapeutic potential of this finding was explored using T cells isolated from colorectal cancer patients. The findings were striking and indicated that blockade of CD59 significantly enhanced the CD4(+) T cell response to two different tumor Ags. These data highlight the potential for manipulating CD59 expression on T cells for boosting weak immune responses, such as those found in individuals with cancer.
Sivasankar
Baalasubramanian
B
Department of Medical Biochemistry and Immunology, Henry Wellcome Building, School of Medicine, Cardiff University, Heath Park, Cardiff, UK.
Longhi
M Paula
MP
Gallagher
Kathleen M E
KM
Betts
Gareth J
GJ
Morgan
B Paul
BP
Godkin
Andrew J
AJ
Gallimore
Awen M
AM
D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018957:CD59 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D020298:U937 Cells; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000951:Antigens, Neoplasm; D018957:CD59 Antigens; D018984:Epitopes, T-Lymphocyte; C051590:CD59 protein, human