Year: 2004
Type: letter
Abstract: Transgene-specific tolerance versus immune responseWe read with great interest the article by Morris et al demonstrating the appearance of cytotoxic T lymphocytes specific to a transgene protein in baboons following myeloablative conditioning and transplantation of cytokine mobilized bone marrow (BM)-derived immunoselected CD34 ϩ cells transduced with a human lentiviral vector. 1 Morris et al find no long-term marking and conclude that induction of the transgene-specific immune responses after transplantation may be due to the use of lentiviral vectors as opposed to oncoretroviral vectors.We believe this interpretation is overly simplistic.Our studies with lentiviral vectors in rhesus macaques demonstrate long-term marking without immune responses to the transgene.Contrary to the experience of Morris et al, our animals that underwent transplantation continue to maintain enhanced green fluorescent protein (EGFP) expression levels for nearly 6 years to date at the same levels as originally detected.For example, we have seen no change in expression in an animal who had undergone transplantation more than 5 years ago with a first-generation lentiviral vector (Figure 1A) and have several animals over 1 year after transplantation at the 5% level (Figure 1B-C) using a third-generation human self-inactivating lentiviral vector (An et al 2,3 ; and R.E.D. and I.S.Y.C., unpublished data, 2004).Not only do we not see evidence of any immune response, but we are also unable to elicit an immune response to the transgene product following active immunization, indicating a state of tolerance.4 Although not discussed in the paper by Morris et al, the discrepancy with our findings likely reflects a difference in source of CD34 ϩ cells.They use cytokine-mobilized BM CD34 ϩ cells, whereas we use cytokine-mobilized peripheral blood (PB) CD34 ϩ cells.Indeed, we observed that cytokinemobilized BM CD34 ϩ cells contributed little to long-term engraftment, 3 consistent with their results.On the other hand, even with a lower transduction efficiency (15%-20% evaluated immediately following transduction), 3,5 cytokine-mobilized PB
Source: Blood
Authors: Robert E. Donahue, Irvin S. Y. Chen
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2077577682