Peripheral naïve CD8+ T cells express RO4929097 research buy membrane CD127 at intermediate/high levels and downregulate it upon antigen priming, whereas memory CD8+ T cells express it at high levels [[5]]. In addition to the antigen, a

series of activating stimuli can induce CD127 downmodulation in CD8+ T cells, including IL-2, IL-7, and IL-15 [[6, 7]]. It has been proposed that the few antigen-responding CD8+ T cells that express high CD127 membrane levels at early times during the response are the precursors of long-lived memory CD8+ T cells [[5]]. This hypothesis has been confirmed by some but not by other groups [[8, 9]]. We previously demonstrated that membrane CD127 is downmodulated by CD8+ T cells in the BM [[10, 11]]. This was observed both in antigen-specific memory CD8+ T cells, i.e. OT-I cells primed against ovalbumin [[10]], and in memory-phenotype cells, that is CD44high

CD8+ T cells. In untreated C57BL/6 (B6) mice, we found that BM CD44high CD8+ T cells contained a lower percentage of CD127+ cells, as compared with both CD44high CD8+ T cells in spleen and lymph nodes (LNs) and CD44int/low CD8+ T cells in the BM [[11]]. Our CD127 findings become more meaningful in the frame of our and others’ results, showing that the BM is a crucial organ for memory CD8+ T-cell activation and maintenance [[10, 12-16]]. Indeed, we previously showed that at any given time a higher percentage of BM memory CD8+ T cells proliferates within learn more this organ, as compared with corresponding cell percentages in spleen and LNs [[10, 11]]. Moreover, we documented that CD8+ T cells are in a more activated state in the BM than in spleen and LNs [[11, 17]]. In human patients with viral infections, autoimmune diseases and cancers, BM CD8+ T cells are enriched in antigen-specific memory cells, which have a more activated phenotype

as compared with the corresponding cells in blood [[18]] and referred to in [[16]]. In addition, BM CD8+ T cells from healthy human subjects express higher membrane levels of the activation marker HLA-DR than blood CD8+ T cells Ergoloid [[19]]. The regulation of CD127 expression is important also in the case of T-cell subsets other than CD8+. Indeed, low or negative expression of membrane CD127 is typical of CD4+ CD25+ FoxP3+ Treg cells [[20]]. In HIV-infected patients, both CD4+ and CD8+ blood T cells have a decreased CD127 expression as compared with those in healthy subjects [[21]]; this might impair immunological recovery in course of highly active antiretroviral therapy [[22]]. Genetic studies on human CD127 polymorphism demonstrated unexpected associations between CD127 variants and risk of some immune-mediated diseases, such as multiple sclerosis and type I diabetes [[23, 24]]. Thus, a better understanding of the mechanisms regulating the IL-7/CD127 axis is needed in the light of potential applications in human diseases.