Immunodeficient nonobese diabetic-severe combined immunodeficiency-IL-2 receptor γ<sup>null</sup> mice were injected with human peripheral blood mononuclear cells, and subsequently injected with the CD39/CD73 antagonist αβ-methylene-ADP (APCP) (50 mg kg<sup>-1</sup> ) or saline for 7 days, or the AR antagonist caffeine (10 mg kg<sup>-1</sup> ) or saline for 14 days.
Notably, PGE<sub>2</sub> increased transduction of repopulating human HSPCs in an immune-deficient (nonobese diabetic/severe combined immunodeficiency/interleukin-2 gamma receptor null [NSG]) xenotransplantation mouse model without evidence of in vivo toxicity, lineage bias, or a de novo bias of lentiviral integration sites.
We also showed that SCID NK cells could be activated to produce perforin, and perforin production was greatly enhanced in NK cells from both SCID and non-SCID pigs after IL-2 cytokine treatment.
The CD56(neg) FC subpopulation significantly promotes homing of HSPCs to BM in nonobese diabetic/severe combined immunodeficiency/IL-2 receptor γ-chain knockout mouse recipients and enhances hematopoietic colony formation in vitro.
Finally, non-obese diabetic/severe combined immunodeficiency mice xenografted with RS 4:11 cells had a significant increase in survival (P < 0.02) in mice treated with romidepsin and interleukin-2-activated NK cells compared with each of these other treatment groups.
Patients with T⁺/low NK⁺ IL-2 receptor γ chain deficiency have differentially-impaired cytokine signaling resulting in severe combined immunodeficiency.
All had a vaccine-injection scar except for one with lower CD3 and natural killer cells, compatible with severe combined immunodeficiency (SCID) identified by IL-2 receptor common gamma chain (IL2RG) mutation (Arg226Lys).
Defective expression of the interleukin-2/interleukin-15 receptor beta subunit leads to a natural killer cell-deficient form of severe combined immunodeficiency.
A report by French physician-scientists suggests a successful application of gene transfer methods in the treatment of two children with severe combined immunodeficiency (SCID) due to defective interleukin 2 receptor common gamma chain.
A novel mutant gammac chain from a patient with typical phenotype of X-linked severe combined immunodeficiency (SCID) has partial signalling function for mediating IL-2 and IL-4 receptor action.
Moreover, recent reports have added to our knowledge on their highly specific functions: JAK3 knockout mice and JAK3 deficient patients cannot signal through the interleukin-2,4,7,9, or 15 receptors and suffer from severe combined immunodeficiency (SCID).
The phenotypic differences between X-SCID and IL-2-deficient SCID suggests that the IL-2Rgamma chain might be a component of other receptors needed for thymic development, B cell class-switching, and NK development.
IL2RG, the gene encoding the common gamma chain, gamma c, of the receptor for interleukin-2 and other cytokines, has been identified as the disease gene for severe combined immunodeficiency (SCID) of the X-linked type.
Adoptive transfer of syngeneic tissue-derived T cells, but not of peripheral blood T cells, into engrafted SCID mice enhanced the transcription of IL-2 and IFN-gamma in the implanted arteries.
Severe combined immunodeficiency (SCID) with a normal number of B-lymphocytes usually demonstrates an X-linked inheritance and now is regarded as an interleukin-2-receptor (IL-2R) gamma-chain gene defect.
Following retroviral-mediated gene transfer of gamma c into SCID X1 bone marrow progenitors, it was possible to reproduce a similar pattern of NK cell differentiation in two SCID-X1 patients with SCF + IL-2 + IL-7 and more efficiently in one of them with SCF + IL-15.
Mutation of the gamma c chain common to interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL-15 receptors has been shown to be responsible for the X chromosome-linked severe combined immune deficiency (SCIDX1).
The IL2RG gene encoding the gamma chain of the lymphocyte receptor for IL-2 lies in human Xq13.1 and is mutated in males with X-linked severe combined immunodeficiency (SCID).
Human severe combined immunodeficiency (SCID), a syndrome of profoundly impaired cellular and humoral immunity, is most commonly caused by mutations in the X-linked gene for interleukin-2 (IL-2) receptor gamma chain (IL2RG).
X-linked severe combined immunodeficiency (SCID) is characterized by profound defects in cellular and humoral immunity and, in humans, is associated with mutations in the gene for the gamma chain of the IL-2 receptor (IL-2R gamma).
These represent the first human disease phenotypes associated with three gene families already recognized to be important in lymphocyte development and signaling: XLA is caused by mutations of a B-cell specific intracellular tyrosine kinase; HIGM by mutations in the tumor necrosis factor-related CD40 ligand, through which T cells deliver helper signals by direct contact with B-cell CD40; and SCID by mutations in the gamma chain of the lymphocyte receptor for interleukin-2.
X chromosome-linked severe combined immunodeficiency disease (SCIDX1) is characterized by the absence of T-cell and natural killer cell development and results from molecular mutations of the interleukin 2 receptor (IL-2R) gamma chain.
The discovery that this disease results from the mutations of the IL-2R gamma chain was surprising since IL-2-deficient mice and human SCID patients had milder phenotypes.