A non-human primate model for analysis of safety, persistence, and function of adoptively transferred T cells.
BACKGROUND
Adoptive immunotherapy with antigen-specific effector T-cell (T(E) ) clones is often limited by poor survival of the transferred cells. We describe here a Macaca nemestrina model for studying transfer of T-cell immunity.


METHODS
We derived, expanded, and genetically marked CMV-specific CD8(+) T(E) clones with surface markers expressed on B cells. T(E) cells were adoptively transferred, and toxicity, persistence, retention of introduced cell-surface markers, and phenotype of the persisting T cells were evaluated.


RESULTS
CD8(+) T(E) clones were efficiently isolated from distinct memory precursors and gene-marking with CD19 or CD20 permitted in vivo tracking by quantitative PCR. CD19 was a more stable surface marker for tracking cells in vivo and was used to re-isolate cells for functional analysis. Clonally derived CD8(+) T(E) cells differentiated in vivo to phenotypically and functionally heterogeneous memory T-cell subsets.


CONCLUSIONS
These studies demonstrate the utility of Macaca nemestrina for establishing principles for T-cell therapeutics applicable to humans.
Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. cberger@fhcrc.org
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D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D018929:Cell Culture Techniques; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000382:microbiology; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D008254:Macaca nemestrina / Q000276:immunology*; D023421:Models, Animal; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D016133:Polymerase Chain Reaction
D018941:Antigens, CD19; D018951:Antigens, CD20