Abstract
Memory T cell populations allow a rapid immune response to pathogens that have been previously encountered and thus form the basis of success in vaccinations. However, the molecular pathways underlying the development and maintenance of these cells are only starting to be unveiled. Memory T cells have the capacity to self renew as do hematopoietic stem cells, and overlapping gene expression profiles suggested that these cells might use the same self-renewal pathways. The transcription factor Hoxb4 has been shown to promote self-renewal divisions of hematopoietic stem cells resulting in an expansion of these cells. In this study we investigated whether overexpression of Hoxb4 could provide an advantage to CD4 memory phenotype T cells in engrafting the niche of T cell deficient mice following adoptive transfer. Competitive transplantation experiments demonstrated that CD4 memory phenotype T cells derived from mice transgenic for Hoxb4 contributed overall less to the repopulation of the lymphoid organs than wild type CD4 memory phenotype T cells after two months. These proportions were relatively maintained following serial transplantation in secondary and tertiary mice. Interestingly, a significantly higher percentage of the Hoxb4 CD4 memory phenotype T cell population expressed the CD62L and Ly6C surface markers, characteristic for central memory T cells, after homeostatic proliferation. Thus Hoxb4 favours the maintenance and increase of the CD4 central memory phenotype T cell population. These cells are more stem cell like and might eventually lead to an advantage of Hoxb4 T cells after subjecting the cells to additional rounds of proliferation.
Highlights
Memory T cells develop from a small subset of effector T cells following a primary immune response
To validate the expression of the transgene in memory phenotype (MP) T cell populations, Quantitative Reverse Transcriptase (Q-RT)-PCR for Hoxb4 was performed on RNA purified from CD4 and CD8 T cell subpopulations sorted from lymph nodes (LNs) and spleen of adult Hoxb4 transgenic and wt mice
Memory T cells are triggered to proliferate following the transplantation into a lymphopenic host through increased availability of IL-7 and likely IL-15 [3,6]
Summary
Memory T cells develop from a small subset of effector T cells following a primary immune response. In addition to IL-7 and IL-15, which are the key factors for the survival and homeostatic proliferation of memory T cells, other cytokines have been shown to boost their homeostatic proliferation, such as IL-2 and interferon-1 (IFN-I) [11,12,13] Despite their independence for T cell receptor (TCR) signalling to survive, experiments using knock-out mice showed that antigen specific CD4 memory T cells had reduced responses to antigen re-encounter in the absence of major histocompatibility complex (MHC) II [14]. The presence of MHC II signals influenced the homeostatic expansion capacity of memory T cells under lymphopenic conditions, but this appeared to be independent on the avidity for MHC II, in contrast to naıve T cells [15]. This suggests that regulatory mechanisms governing memory homeostasis are different from naıve T cell homeostasis, which is important to maintain optimal diversity of the memory pool
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