Memory lapses in graft-versus-host disease

"Faster, better, more" is the conventional benchmark used to define responses of memory T cells when compared with their naïve counterparts. In this issue of the European Journal of Immunology, Mark and Warren Shlomchik and colleagues [Eur. J. Immunol. 2011. 41: 2782-2792] make the intriguing observation that murine memory CD4(+) T-cell populations enriched for alloreactive precursors are fully capable of rejecting allogeneic skin grafts but yet are incapable of inducing significant graft-versus-host disease. These observations add to the emerging concept that memory CD4(+) T-cell development is more nuanced and complex than predicted by conventional models. In particular, the data suggest that it may be just as important to consider what naïve or effector cells have "lost" in their transition to memory.