**Conflict of interest**

*Cells of the Immune System*

Further, T- and B-cell receptor repertoire gene arrangements can be evaluated by molecular techniques such as next generation sequencing [116, 117]. Michalek et al. [118] have demonstrated β chain sequencing of the T-cell receptor in order to identify the T-cell clones that could mediate either graft-versus-host disease or graft-versus-leukemia effect. Brink et al. [9] reported higher diversity in CD4+ T cells than CD8+ T cells following allogeneic HSCT. Greater diversity was observed in cord blood grafts, followed by unmanipulated grafts and T-cell depleted grafts.

Many strategies, such as administration of recombinant cytokines, adoptive cell therapy, and hormone-based therapies, have recently been used to improve immune

IL7 cytokine has been shown to effectively enhance reconstitution of T and B lymphoid cells by enabling thymopoiesis [105, 119]. It has been demonstrated that IL7 increased the CD3+, CD4+, and CD8+ T-cell levels to more than four folds and also leads to increase in functional and diverse T cells [120]. Administering IL-7 predominantly increases the naïve CD8+ T cells. The timing of administering is, however, important, as administering early after transplant aggravates GvHD [116, 121], whereas administering it at a later stage after HSCT results in lower risk of GvHD. This is contributed by the activation of alloreactive T cells that express lower IL-7Rα levels [32, 38]. Other cytokines that enable immune reconstitution are insulin-like growth factor 1(IGF-1), IL22, IL15, and IL12 [122–124]. IL15 has been shown to significantly increase the reconstitution of CD8+ T cells and NK cells and improve the GvL effect in haploidentical murine models [125]. Sauter et al. [126] reported better lymphocyte reconstitution after IL-15 administration in T-cell depleted allogeneic HSCT; however, it has been shown to worsen GvHD.

Recently, it has been suggested that modulating the function of dendritic cells could reduce GvHD while maximizing GvL [127]. Studies on reconstitution of dendritic cells after HSCT have been contradictory. Maraskovsky et al. [128] have shown that treatment with Flt3-L can expand DC subsets; however, when administered after HSCT, it can worsen GvHD [38]. Gauthier et al. [38] have demonstrated that SDF-1α therapy can expand the DC1 subsets and lower the severity of GvHD. Because of their immunosuppressive properties, mesenchymal stem cells have recently been used for suppressing GvHD [129–131]. Mesenchymal stem cells release cytokines such as IL-7, which improve T-cell survival and promote reconsti-

NK-cell immunotherapy is one of the novel strategies underway to reduce GvHD and enhance graft-versus-leukemia effect in a KIR-HLA mismatched haploidentical

Recently, few studies have identified the association of reconstitution of certain

immune subsets with predicting post-HSCT outcomes. However, these studies are often limited by small sample size, lack of detailed immune reconstitution, and secretome profile, which could be used as biomarkers to predict immune reconstitution. Prospective studies involving a large number of patients should be conducted to determine which immune factors and tests to detect the same could have prognostic value and understand the impact of such predictive risk factors on transplant outcomes. This is most beneficial, especially for recipients of

**5. Strategies to improve immune reconstitution**

tution of dendritic cells by secreting SDF-1α [132].

reconstitution after transplantation.

**198**

HSCT [133–135].

**6. Future directions**

The authors declare no conflict of interest.
