| First Author | van Rijn RS | Year | 2007 |
| Journal | Exp Hematol | Volume | 35 |
| Issue | 1 | Pages | 117-27 |
| PubMed ID | 17198880 | Mgi Jnum | J:123194 |
| Mgi Id | MGI:3717333 | Doi | 10.1016/j.exphem.2006.09.018 |
| Citation | van Rijn RS, et al. (2007) Quantitative assessment of human T lymphocytes in RAG2(-/-)gammac(-/-) mice: the impact of ex vivo manipulation on in vivo functionality. Exp Hematol 35(1):117-27 |
| abstractText | OBJECTIVE: Recent clinical trials of adoptive immunotherapy showed diminished reactivity of human T cells upon ex vivo manipulation. For a safe and effective clinical application of human T cells, it is necessary to improve ex vivo manipulation procedures and evaluate their impact on in vivo functionality. However, there is no preclinical model for quantitative assessment of in vivo functionality of human T cells. In this study, we investigated the feasibility of using the huPBMC- RAG2(-/-)gammac(-/-) xenogeneic mouse model. As a first example, we compared 3 different ex vivo culture conditions for human T cells. METHODS: RAG2(-/-)gammac(-/-) mice received cultured human T cells that were stimulated via CD3 alone or costimulated via CD28 (CD3/28) and/or human 4-1BB (CD3/28/4-1BB). Engraftment levels and survival of the cells were measured. The dynamics of the human T cell phenotypes were analyzed during culture and in vivo, as well as the mechanism of the xenoresponse. RESULTS: Engraftment potential was improved twofold for costimulation compared to CD3 alone (p < 0.001). Phenotypic analysis showed a strikingly similar pattern of development towards CD4(+) and CD8(+) effector and effector-memory cells, suggesting antigen-driven survival and expansion. All parameters used to analyze different effects on in vivo T-cell functionality, like culture condition, engraftment levels, survival of the cells over time, or xenogeneic graft-vs-host disease were absolutely independent of the distribution of the T cell population in vivo following contact with xeno-antigen. CONCLUSION: The huPBMC-RAG2(-/-)gammac(-/-) xenogeneic transplant model is the most sensitive to date for in vivo functional evaluation of human T cells. |
