Table 2 |.

Human immunodeficiencies that are potentially treatable with IL-7 therapy

Clinical condition	Specific populations predicted to benefit from rhIL-7	Promise	Pitfalls
HIV infection	Immune non-responders: these individuals have persistent severe CD4+ T cell depletion after viral suppression with HAART and have increased mortality rates compared with patients with CD4+ T cell reconstitution after HAART129–131	Early results show persistent increases in CD4+ T cell counts even after short-course IL-7 administration. Concomitant HAART seems to prevent IL-7-induced increases in viral load	Large studies will be needed to determine whether IL-7-induced increases in CD4+ T cell counts translate into increased survival and/or decreased mortality
Idiopathic CD4+ T cell lymphocytopaenia	Individuals with opportunistic infections and/or significant morbidity and mortality associated with CD4+ T cell deficiency	IL-7 therapy is predicted to increase CD4+ T cell counts	Rare, heterogeneous population of patients, who are difficult to study systematically
Congenital immunodeficiency	Individuals with incomplete DiGeorge syndrome or other subsets of patients with a ‘leaky phenotype’such that some T cells are present; this T cell population could be expanded with rhIL-7	IL-7 therapy is predicted to increase the size of T cell subsets, particularly of naive recent thymic emigrants	• Not likely to benefit patients with a complete block in T cell development • Potential increased risk of Omenn syndrome, a GVH D-like autoimmune condition in patients with congenital immunodeficiency
After haematopoietic stem cell transplantation	Individuals who receive profoundly T cell-depleted stem cell transplants following haploidenticaltransplantation and patients who receive an umbilical cord blood transplant who have slow and incomplete immune reconstitution. Impaired immune reconstitution correlates with increased post-transplant morbidity and mortality132	IL-7 therapy is predicted to increase the rate and degree of T cell reconstitution	Potential increased risk of GVHD, EBV-associated lymphoproliferation or graft rejection
After chemotherapy for cancer	Individuals who receive dose-intensive lymphotoxic agents, particularly with increased age and mediastinal irradiation	IL-7 therapy is predicted to increase the rate and degree of T cell reconstitution	• Careful clinical studies of targeted populations will be needed to determine whether enhanced immune reconstitution translates into improved overall or event-free survival • IL-7-mediated signalling on leukaemias and lymphomas precludes its use in this high-risk population
Ageing	Elderly individuals who are poor responders to vaccines and are susceptible to viral reactivation	Even short-term IL-7 therapy is predicted to enhance TCR repertoire diversity through the preferential proliferation of recent thymic emigrants and naive T cells. Combining IL-7 with vaccines might increase the probability of a vaccine response	Careful clinical studies will be needed to determine whether improved immune parameters translate into improved survival or decreased infection-related morbidity or mortality

EBV, Epstein–Barr virus; GVHD, graft-versus-host disease; HAART, highly active antiretroviral therapy; rhIL-7, recombinant human interleukin-7; TCR, T cell receptor.