Enhancing alloreactivity does not restore GVHD induction but augments skin graft rejection by CD4⁺ effector memory T cells.

Graft-versus-host disease (GVHD) caused by donor T cells attacking recipient tissues is a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (alloSCT). Studies have shown that effector memory T (T(EM) ) cells do not cause GVHD but are capable of immune functions post-transplant, including graft-versus-leukemia (GVL) effects, but the reasons for this are unclear. In mice, the T(EM) pool may have a less diverse T-cell receptor (TCR) repertoire than naive T (T(N) ) cells with fewer alloreactive clones.

CTLA4 expression is an indicator and regulator of steady-state CD4+ FoxP3+ T cell homeostasis.

The presence of FoxP3(+) regulatory T cells (Tregs) is necessary for control of deleterious immune responses in the steady state; however, mechanisms for maintaining the frequency and quality of endogenous Tregs are not well defined. In this study, we used in vivo modulators of the CD28 and CTLA4 pathways administered to intact mice to reveal mechanisms controlling the homeostasis and phenotype of endogenous Tregs. We demonstrate that expression of the negative costimulatory regulator CTLA4 on FoxP3(+) Tregs in vivo is a direct consequence of their rapid, perpetual homeostasis.

Generation, homeostasis, and regulation of memory T cells in transplantation.

Purpose Of Review: Sensitized individuals experience higher rates of acute rejection and decreased graft survival. Memory T cells have been implicated in these processes, and in the prevention of tolerance induction. A greater understanding of T-cell memory generation, maintenance, and regulation is needed to design new immunosuppressive strategies that prolong graft survival in the presence of alloreactive memory.

Reshaping the past: Strategies for modulating T-cell memory immune responses.

Memory T cells are generated following an initial encounter with antigen, persist over the lifetime of an individual, and mediate rapid and robust functional responses upon antigenic recall. While immune memory is generally associated with protective immune response to pathogens, memory T cells can be generated to diverse types of antigens including autoantigens and alloantigens through homologous or crossreactive priming and comprise the majority of circulating T cells during adulthood. Memory T cells can therefore play critical roles in propagating and perpetuating autoimmune disease and in mediating allograft rejection, although the precise pathways for regulation of memory immune responses remain largely undefined.