Volume 8 Supplement 1
HTLV-1 propels thymic human T cell development in “human immune system” Rag2-/- IL-2R γc-/- Mice
© Villaudy et al; licensee BioMed Central Ltd. 2011
Published: 6 June 2011
Alteration of early haematopoietic development is thought to be responsible for the onset of immature leukemias and lymphomas. We have previously shown that HTLV-1 (Human T cell Leukemia Virus type 1) is able not only to infect immature thymocytes in vitro but also, through Tax expression, to alter the β-selection checkpoint critical for early T cell development. To further clarify the role of the natural HTLV-1 infection on human T-cell development, we developed an in vivo model by transplanting immunocompromised Rag2-/-γc-/- newborn mice with human cord blood CD34+ cells to obtain Human Immune System (HIS) mice. In these mice the development of human T cells in the thymus is fully developed within two months after human cell transplantation. Lethally irradiated HTLV-1 producing cells were then injected into these HIS mice. Herein we observed in the thymus of the infected animals an enlarged population of mature T cells when compared with the mock-infected mice. Furthermore, we noted an increased number of CD4+ cells expressing CD25. Infected animals also developed, several weeks after the infection, pathological features such as splenomegaly, adenopathy, thymomas, lymphomas and leukemias in which predominate human T cells, with a large proportion of CD25+ activated cells. Tax expression especially in the lymphomas and thymomas correlated with an up-regulation of NF-κB regulated genes. Altogether, these results underline that this HIS Rag2-/-γc-/- model might be of great interest to study the leukemogenic process induced by HTLV-1 as well as to validate new therapeutic approaches of ATL.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.