A novel model system for the study of anti-tumour T-cell memory

An adoptive immunotherapy (ADI) protocol was developed where the fate and requirements of longterm persisting memory T-cells can be monitored. Anti-tumour immune peritoneal exudate cells (iPEC) were produced by injecting a subtumorigenic dose of the highly metastatic, ß-gal⁺ T-Iymphoma into the ear pinna of syngeneic DBN2 mice, followed by an intraperitoneal challenge with irradiation-inactivated tumour cells. 33.9 % of CD8⁺ iPEC were shown to be recognising the immunodominant peptide of ß-gal (aa 876-884), and, consistently, the iPEC exerted specific lysis of ß-gal⁺ cells. Upon adoptive transfer into sublethally irradiated, ESbL-Gal tumour-bearing, athymic Balb/c nu/nu mice, they conferred protective and long-lasting anti-tumour immunity. ADI-treated animals were able to reject subsequent high dose tumour challenges, and memory T-cells appeared to be only partially affected by y-irradiation. ß-gaI^876-884 peptide/MHC class I tetramer stainings identified the bone marrow as the major compartment for the long-term persistence of memory T-cells, as ß-gaI^876-884 specific T -cells occurred at elevated frequencies in this microenvironment as compared to the spleen and lymph nodes. In a "parking experiment", Agremoval led to a decrease of tetramer-binding cells below background levels. Tumour-reactive memory T-cells could be reisolated from AD I-treated animals by recruitment to the peritoneal cavity via Ag-specific challenge at this anatomical site. Reisolated memory PEC (mPEC) retained their reactivity and conferred tumour protection even after multiple transfers to subsequent tumour bearing nude mice.<br></br><br></br>The present model proved to be a valuable tool for the evaluation of the factors and mechanisms involved in the long-term maintenance of T-cell memory, and promises to yield further invaluable data in this field of research.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

The Open University

Year dc:date.issued

2001

Author dc:creator

• Mahnke, Yolanda Dagmar

Language dc:language

en