A repertoire independent and cell intrinsic defect in murine GVHD induction by effector memory T cells (169.6)
| Autor: | Kathryn Juchem, Britt Anderson, Cuiling Zhang, Jennifer McNiff, Anthony Demetris, Andrew Caton, Warren Shlomchik, Mark Shlomchik |
|---|---|
| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:169.6-169.6 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Graft versus host disease (GVHD) is a major complication of allogeneic stem cell transplantation (alloSCT). In murine models of alloSCT, naïve T cells (TN) cause GVHD, while effector memory T cells (TEM) do not. Why TEM fail to cause GVHD is unknown and whether central memory T cells (TCM) are also unable to cause GVHD is controversial. It has been proposed that a more-restricted T cell receptor repertoire within the memory T cell (TM) pool may limit the ability of TM to recognize alloantigens. To address the role of repertoire, we developed a novel T cell receptor transgenic (Tg) GVHD model in which naive CD4+ TS1 Tg T cells, which recognize an epitope of influenza hemagglutinin (HA), are transferred, along with syngeneic bone marrow, into irradiated transgenic recipients that ubiquitously express HA. We then converted TS1 TN to TM and tested these for GVHD induction. TEM caused minimal, transient GVHD whereas TN and TCM caused potent GVHD. TEM engrafted and accumulated in the spleen to the same extent as TN, but failed to accumulate in the colon. Within the colon, TEM were dividing less actively than TN, and in co-transfer experiments TN out-competed TEM. TEM induced GVHD in recipients that lack expression of PD-L1 and PD-L2, indicating that PD-1, which is unregulated on TS1 cells post transplant, limits the ability of TEM to induce GVHD. Thus, cell intrinsic properties independent of repertoire explain the impairment of TEM while TCM clearly can cause GVHD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|