X-Linked Immunodeficiencies

Puck, Jennifer M.

doi:10.1007/978-1-4615-3010-7_2

Cited by 11 publications

(11 citation statements)

References 82 publications

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“…In the human disease the defect in T cell development is more severe, while the production of B cells is outwardly normal. Nevertheless, the resulting IgM-bearing B lymphocytes exhibit restricted function due to the lack of T helper activity and to undefined developmental defects as uncovered by analysis of inactivation patterns of the X chromosome in carrier females [12].…”

Section: Introductionmentioning

confidence: 99%

Monoclonal antibodies to the common γ-chain as cytokine receptor antagonists in vivo: effect on intrathymic and intestinal intraepithelial T lymphocyte development

Malek

Levy²,

Adkins

et al. 1998

Journal of Leukocyte Biology

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Mice lacking a functional ␥c subunit of cytokine receptors exhibit profound defects in the development of multiple lymphoid lineages. To investigate the role of ␥c-dependent cytokines in T cell development, the phenotype of developing T cells was compared in interleukin (IL)-7R␣-deficient mice and anti-␥c mAb-treated chimeric mice reconstituted with adult bone marrow cells or subsets of pro-T cells. These studies indicate that ␥c contributes to T cell development at multiple stages of pro-T cell maturation and that IL-7/IL-7R is the primary cytokine for thymic-dependent T cell development. However, our data also implicate other ␥c-dependent cytokines during thymic T cell development. By contrast, substantial intestinal intraepithelial lymphocytes (IEL) development was observed in the intestinal intraepithelium in both types of mice. Analysis of IL-7R␣-deficient mice indicates that the IL-7/IL-7R system is critical only for the development of TCR ␥␦ ؉ IEL. However, the inhibitory activity of the anti-␥c mAb in the chimeric mouse model suggests that additional ␥c-utilizing cytokines regulate the development of the remaining subsets of IEL.

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Section: Introductionmentioning

confidence: 99%

Monoclonal antibodies to the common γ-chain as cytokine receptor antagonists in vivo: effect on intrathymic and intestinal intraepithelial T lymphocyte development

Malek

Levy²,

Adkins

et al. 1998

Journal of Leukocyte Biology

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“…Estimated to occur in 1 in 10,000 to 100,000 births, X-linked' SCID generally has a severe phenotype, with failure to thrive and infections leading to death before 18 mo of age unless successfully treated by bone marrow transplantation (3,4). Patients have very few T cells and absent mitogen responses; although B cells are often present, immunoglobulin levels are low, and specific antibody production is lacking.…”

Section: Introductionmentioning

confidence: 99%

Female germ line mosaicism as the origin of a unique IL-2 receptor gamma-chain mutation causing X-linked severe combined immunodeficiency.

Puck

Pepper²,

Bédard³

et al. 1995

J. Clin. Invest.

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The IL2RG gene encoding the y chain of the lymphocyte receptor for IL-2 lies in human Xql3.1 and is mutated in males with X-linked severe combined immunodeficiency (SCID). In a large Canadian pedigree genetic linkage studies demonstrated that the proband's grandmother was the source of an X-linked SCID mutation. However, her T cells did not show the expected skewed X chromosome inactivation pattern of female'carriers of SCID, despite her having one affected son and two carrier daughters with skewed X inactivation. Single strand conformation polymorphism analysis of IL2RG in the affected proband was abnormal in exon 5; sequencing revealed a nine nucleotide in-frame duplication insertion. The three duplicated amino acids included the first tryptophan of the "WSXWS" motif found in all members of the cytokine receptor gene superfamily. Mutation detection in the pedigree confirmed that the founder' grandmother's somatic cells had only normal IL2RG, and further showed that the SC1D-associated X chromosome haplotype was inherited by three daughters, one with a wild type IL2RG gene and two others with the insertional mutation. Female germ line mosaicism is unusual, but its presence in this X-linked SCID family emphasizes the limitations of genetic diagnosis by linkage as compared with direct mutation analysis. (J. Cln. Invest 1995. 95:895-899.)

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“…Evidence for clinical heterogeneity has been provided by the demonstration that the HIM syndrome can be either occur as a primary or as an acquired disorder (2,3). Primary HIM is a very rare disease, which accounts for as little as 0.3-2.0% of all primary immunodeficiencies (4).…”

Section: Introductionmentioning

confidence: 99%

“…However, occurrence in females suggest that primary HIM syndrome can also be inherited as an autosomaldominant transmission (1,3). Immune abnormalities in HIM syndrome are in most cases restricted to B cells with secretion of IgM only (5,6).…”

Section: Introductionmentioning

confidence: 99%

Signaling through CD40 rescues IgE but not IgG or IgA secretion in X-linked immunodeficiency with hyper-IgM.

Saiki

Tanaka²,

Wada³

et al. 1995

J. Clin. Invest.

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The ligand for CD40 (CD40L) is a membrane protein on activated T cells that induces B cell proliferation and differentiation. Several mutations of the CD40L gene were reported responsible for defective class switching of B cells in an X-linked immunodeficiency with hyper IgM (X-HIM).We studied four affected males from three families and found three independent mutations including new mutations of CD40L gene. In every X-HIM patient tested, however, anti-CD40 plus IL-10 did not induce class switching from IgM to IgG or IgA, even in the presence of Staphylococcus aureus Cowan I strain (SAC). CD4+ T cell clones, expressing CD40L on their surface, also did not rescue IgG or IgA induction by X-HIM peripheral blood B cells in vitro. But signaling through CD40 induced both B cell proliferation and IgE secretion when IL-4 was added to the culture.Taken together, these results show that in vitro signaling through CD40 rescues IgE but not IgG or IgA secretion by peripheral blood X-HIM B cells and suggest that in vivo CD40 and CD4OL interaction might be necessary for IgG and IgA differentiation in X-HIM. (J. Clin. Invest. 1995. 95:510-514.)

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X-Linked Immunodeficiencies

Cited by 11 publications

References 82 publications

Monoclonal antibodies to the common γ-chain as cytokine receptor antagonists in vivo: effect on intrathymic and intestinal intraepithelial T lymphocyte development

Monoclonal antibodies to the common γ-chain as cytokine receptor antagonists in vivo: effect on intrathymic and intestinal intraepithelial T lymphocyte development

Female germ line mosaicism as the origin of a unique IL-2 receptor gamma-chain mutation causing X-linked severe combined immunodeficiency.

Signaling through CD40 rescues IgE but not IgG or IgA secretion in X-linked immunodeficiency with hyper-IgM.

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