It is established that the thymus undergoes a physiological involution with aging that affects its structure and environment. However, studies in the 1980s documented lymphocytic thymic tissue in adults up to 107 years of age.
Moreover, several studies suggested that the human thymus could continue to mature new T cells throughout life, proved by the presence of signal-joint T-cell receptor excision circle (sjTREC) bearing T cells into the peripheral blood even in elderly individuals. T-cell recovery after allogeneic transplantation following myeloablative (high dose) or reduced intensitive/non-myeloablative conditionings depends on both peripheral expansion of mature T cells contained in the graft (thymo-independent pathway), and T-cell neo-production from donor hematopoietic stem cells (thymodependent pathway). In young patients, most circulating T cells during the first 3- 6 months following transplant are the progeny of T cells infused with the grafts, whereas neogeneration of T cells by the thymus plays an important role in reconstituting the Tcell pool beyond day 100 after transplant. The aim of this project is that of analyzing the immune recovery, in particolar the T cell compartment and the thymic function, after different conditionings in different patient cohorts stratified by age. Moreover, laboratory data will be correlated with disease response, graft-vs.-host disease and incidence of opportunistic infections.
By flow cytometry. naïve, central memory, effector memory, and “revertant” CD4+ T cells are identified by co-expression of CD45RA and CD27, CD45RO and CD27, expression of CD45RO (CD27 negative), and co-expression of CD45RA and CDRO, respectively. Tregs are identified by CD4+CD25+Foxp3. To quantify residual thymic function, and to differ true naïve CD4+ from “revertant” CD4+ T cells, Tcell receptor rearrangement excision circles (sjTRECs) are measured by real time PCR on DNA extracted from peripheral mononuclear cells and from sorted CD4+ T cells. sjTRECs are circular DNA sequences formed during the process of T cell receptor rearrangement, which are not duplicated but diluted during cell division and therefore a valid estimate of newly formed T cells. TCR repertoire analysis of V-beta families is evaluated by spectratyping as previously described (Mariani et al. Exp Hematol. 2