T follicular helper and memory cell responses and the mTOR pathway in murine heart transplantation
Section snippets
Mice
C57BL/6 (B6), BALB/c, Cd4-Cre, Mtorfl/fl, and Stat3fl/fl mice were purchased from Jackson Laboratory (Bar Harbor, ME). A further description of these mouse strains is listed in Supplementary Table S1 (available online at www.jhltonline.org/). Mtorfl/fl and Stat3fl/fl mice were crossed with Cd4-Cre mice to create Mtorfl/flCd4-Cre, Stat3fl/flCd4-Cre, and Mtorfl/flStat3fl/flCd4-Cre mice. Mice were housed in a specific pathogen-free facility at the Houston Methodist Research Institute in Houston,
The deletion of mTOR in T cells induce long-term heart allograft survival
To determine the role of mTOR in the regulation of T cell responses in transplantation, BALB/c hearts were transplanted into Mtorfl/flCd4-Cre (B6 background) and wild-type (WT) B6 mice. As shown in Figure 1A, none of the Mtorfl/flCd4-Cre mice rejected their BALB/c heart allografts (median survival time [MST] of > 100 days; n = 5), whereas WT B6 mice rejected BALB/c hearts acutely (MST = 8.6 ± 0.55 days; n = 5). The histology of heart allografts harvested from the Mtorfl/flCd4-Cre recipients at
Discussion
The molecular mechanisms underlying allogeneic T cell responses have not been adequately explored. This study found that all heart allografts survived more than 100 days in mice when mTOR was deleted in T cells. Further mechanistic investigation revealed that mTOR in T cells promoted the expansion of CD4+ and CD8+ effector cells. In addition, mTOR was required for the generation of Tfh and GC B cells in response to heart transplantation. Moreover, in skin-sensitized recipients, although mTOR
Disclosure statement
The authors have no conflicts of interest to disclose.
This study was supported by the startup fund from Houston Methodist Research Institute (to W.C.) and the US National Institutes of Health grant (#NIH R01AI132492 to W.C.). The authors would like to thank the Flow Cytometry Core at Houston Methodist for excellent services.
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