Studying Peripheral T Cell Homeostasis in Mice: A Concise Technical Review.

For several years, it was believed that the thymus was entirely responsible for maintaining T cell homeostasis. Today, it is well-known that homeostatic peripheral mechanisms are essential in order to maintain T cell numbers and diversity constant in the periphery. Naïve and memory T cells require continual access to self-peptide MHC class I and II molecules and/or cytokines to survive in the periphery.

IL-7 Is the Limiting Homeostatic Factor that Constrains Homeostatic Proliferation of CD8 T Cells after Allogeneic Stem Cell Transplantation and Graft-versus-Host Disease.

Immune reconstitution after allogeneic hematopoietic stem cell transplantation relies primarily on homeostatic proliferation (HP) of mature T lymphocytes, but this process is typically impaired during graft-versus-host disease (GVHD). We previously showed that low IL-7 levels combined with lack of dendritic cell (DC) regeneration constrain CD4 T cell HP during GVHD. However, it is not clear whether these alterations to the peripheral CD4 T cell niche also contribute to impair CD8 T cell regeneration during GVHD.

Stromal-Derived Factor-1α and Interleukin-7 Treatment Improves Homeostatic Proliferation of Naïve CD4(+) T Cells after Allogeneic Stem Cell Transplantation.

Graft-versus-host disease (GVHD) impairs immune reconstitution after allogeneic stem cell transplantation (allo-SCT) and effective therapies aimed at restoring T cell counts in GVHD patients have yet to be developed. During GVHD, CD4(+) T cell reconstitution is particularly affected and current models hold that GVHD insult to the peripheral lymphoid niche is responsible for this effect. Here, we show that naïve CD4(+) T cell homeostatic proliferation (HP) is lost during GVHD because of low systemic IL-7 and impaired dendritic cell (DC) regeneration.

TCR triggering modulates the responsiveness and homeostatic proliferation of CD4+ thymic emigrants to IL-7 therapy.

Interleukin-7 (IL-7) is currently used in clinical trials to augment T-cell counts. Paradoxically, elevated systemic IL-7 found in lymphopenic humans is typically insufficient for CD4(+) T-cell regeneration, and thymopoiesis becomes critical in this process. Here we show that the proliferative effect of IL-7 is more pronounced on CD4(+)CD8(-) thymocytes compared with peripheral CD4(+) T cells.

SMAD3 prevents graft-versus-host disease by restraining Th1 differentiation and granulocyte-mediated tissue damage.

Gene expression profiling of human donor T cells before allogeneic hematopoietic cell transplantation revealed that expression of selected genes correlated with the occurrence of graft-versus-host disease (GVHD) in recipients. The gene with the best GVHD predictive accuracy was SMAD3, a core component of the transforming growth factor-β signaling pathway, whose expression levels vary more than a 6-fold range in humans. The putative role of SMAD3 in the establishment of graft-host tolerance remained elusive.