Enhanced allostimulatory activity of host antigen-presenting cells in old mice intensifies acute graft-versus-host disease

Differential CD52 expression by distinct myeloid dendritic cell subsets: implications for alemtuzumab activity at the level of antigen presentation in allogeneic graft-host interactions in transplantation

“…Like other studies in this area, [40][41][42] our findings support greater attention to the afferent arm of the immune response, rather than focusing on alloreactive T-cell responders/effectors to the potential exclusion of evaluating antigen presentation. This leads us to hypothesize that the undesirable complications of GVHD or rejection (host-versus-graft) may be distinguishable from the beneficial graft-versus-leukemia or GVT effects exerted by hematopoietic allografts, based on differences in afferent sensitization of an immune response by different types of myeloid DCs.…”

Aging and the immune response to organ transplantation

“…Moreover, DCs from the spleens of old donor mice exhibited increased expression of costimulatory molecules (e.g., CD80, CD86, and CD40) and an enhanced ability to induce antidonor T cell responses in vitro (18). These findings were consistent with a prior study that found that aged DCs induced higher levels of graft-versus-host disease than young DCs (46,47), although direct examination of DCs from aged cardiac allografts was not performed in the former study (18). Assessing tissue-resident immune cells is important for understanding how aging impacts immune responses within organs, as there is an increasing appreciation of the contribution of these cells in maintaining organ homeostasis (18,48,49).…”

Who is the better donor for older hematopoietic transplant recipients: an older-aged sibling or a young, matched unrelated volunteer?

“…Clinical evidence has consistently shown recipient age to be a strong risk factor for development of GVHD, and murine models have attributed this to enhanced allo-stimulatory activity of host antigenpresenting cells in older (when compared with younger) mice. 21,22 Murine data have demonstrated the importance of host antigenpresenting cells and donor effector T cells in the pathophysiology of GVHD. [23][24][25] Because our study addressed the role of donor age in older-age recipients, one would expect that the combination of an older-age recipient and a younger-age donor would indeed result in high rates of GVHD.…”