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Shabbir Hussain

Publications and source records attributed to Shabbir Hussain.

11 recordsLinked to original sources
PubMed2006

Protection from type 1 diabetes by invariant NK T cells requires the activity of CD4+CD25+ regulatory T cells.

Invariant NK T (iNKT) cells regulate immune responses, express NK cell markers and an invariant TCR, and recognize lipid Ags in a CD1d-restricted manner. Previously, we reported that activation of iNKT cells by alpha-galactosylceramide (alpha-GalCer) protects against type 1 diabetes (T1D) in NOD mice via an IL-4-dependent mechanism. To further investigate how iNKT cells protect from T1D, we analyzed whether iNKT cells require the presence of another subset(s) of regulatory T cells (Treg), such as CD4+ CD25+ Treg, for this protection. We found that CD4+ CD25+ T cells from NOD.CD1d(-/-) mice deficient in iNKT cell function similarly in vitro to CD4+ CD25+ T cells from wild-type NOD mice and suppress the proliferation of NOD T responder cells upon alpha-GalCer stimulation. Cotransfer of NOD diabetogenic T cells with CD4+ CD25+ Tregs from NOD mice pretreated with alpha-GalCer demonstrated that activated iNKT cells do not influence the ability of T(regs) to inhibit the transfer of T1D. In contrast, protection from T1D mediated by transfer of activated iNKT cells requires the activity of CD4+ CD25+ T cells, because splenocytes pretreated with alpha-GalCer and then inactivated by anti-CD25 of CD25+ cells did not protect from T1D. Similarly, mice inactivated of CD4+ CD25+ T cells before alpha-GalCer treatment were also not protected from T1D. Our data suggest that CD4+ CD25+ T cells retain their function during iNKT cell activation, and that the activity of CD4+ CD25+ Tregs is required for iNKT cells to transfer protection from T1D.

Animals↗
PubMed2006

Acute urinary retention as a result of a bladder diverticulum.

An 11-month-old infant presented with acute urinary retention. He had presented 3 months earlier with complaints of an enlarging abdominal mass that was initially diagnosed as a mesenteric cyst on ultrasonography. Voiding cystourethrogram revealed a large bladder diverticulum. Bladder diverticulum should be a differential diagnosis in children, especially male, presenting with urinary retention, fever and an abdominal mass.

Acute Disease↗
PubMed2005

A defect in lineage fate decision during fetal thymic invariant NKT cell development may regulate susceptibility to type 1 diabetes.

A numerical and functional deficiency in invariant NKT (iNKT) cells detectable by 3 wk of age in the thymus and spleen mediates the pathogenesis of type 1 diabetes in NOD mice, but the stage of T cell development at which this deficiency first occurs is unknown. We report in this study that this deficiency develops after the CD4(+)CD8(+) double-positive stage of thymic T cell development and is due to a lineage-specific depletion of CD4(-)CD8(-) double-negative alphabeta T cells and iNKT cells from the thymus between embryonic day 18 and day 1 after birth. Thus, an inheritable defect in a lineage fate decision that elicits a deficiency in fetal thymic iNKT cell development may predispose to susceptibility to type 1 diabetes.

Animals↗
PubMed2005

Dysregulated B7-1 and B7-2 expression on nonobese diabetic mouse B cells is associated with increased T cell costimulation and the development of insulitis.

Little is known about the pathogenic role of B cell dysfunction in T cell-mediated autoimmune disease. We previously reported that B cell hyper-responsiveness, resistance to apoptosis, and accumulation in islets occur during the onset of insulitis, but not in type 1 diabetes (T1D), in NOD mice. In this study we extended these studies to further determine how islet-infiltrated B cells contribute to this inflammatory insulitis. We demonstrate the presence of an increased percentage of B7-1(+) and a decreased percentage of B7-2(+) B cells in the spleen of autoimmune disease-prone NOD and nonobese diabetes-resistant mice compared with the spleen of nonautoimmune disease-prone C57BL/6 and BALB/c mice. An age-dependent differential expression of B7-1 and B7-2 was associated with the development of insulitis and CD4(+)CD25(+) T cell deficiency in autoimmune disease-prone mice. Whereas BCR and LPS stimulation increased B7-2 expression on B cells from autoimmune disease-prone and nonautoimmune disease-prone mice, LPS-induced B7-1 expression was higher on NOD than C57BL/6 B cells. Interestingly, increased expression of B7-1 and B7-2 was found on islet-infiltrated B cells, and this increase was associated with enhanced T cell costimulation. Islet-infiltrated B cells were shown to be a source of TNF-alpha production in islets. B7 blockade of BCR-stimulated NOD B cells by anti-B7-1 and anti-B7-2 mAbs during coadoptive transfer with diabetogenic T cells into NOD.scid mice protected these recipients from T1D. These results suggest that increased B7-1 and B7-2 expression on islet-infiltrated NOD B cells is associated with increased T cell costimulation and the development of inflammatory insulitis in NOD mice.

Adoptive Transfer↗
PubMed2005

Role of regulatory invariant CD1d-restricted natural killer T-cells in protection against type 1 diabetes.

Invariant CD1d-restricted natural killer T (iNKT) cells function during innate and adaptive immune responses. A functional and numerical deficiency of iNKT cells is well documented in both nonobese diabetic (NOD) mice and humans with autoimmune type 1 diabetes (T1D). Restoring the numerical and/or functional deficiency of iNKT cells in NOD mice by either treatment with alpha-galactosylceramide, transgenic induction of Valpha14-Jalpha18 expression, or transgenic expression of CD1d in NOD islets under the control of the human insulin promoter confers protection from T1D in these mice. Recently, considerable progress has been made in understanding the developmental and functional activities of iNKT cells. In this review, we discuss the role of iNKT cell deficiency and defective development in the onset of T1D in NOD mice and the different protective mechanisms known to restore these defects.

Animals↗
PubMed2005

Rickets in xeroderma pigmentosum.

Xeroderma pigmentosum patients are advised to strictly avoid sun exposure to prevent ultraviolet-induced DNA damage. We describe a 2 1/2 years old boy having xeroderma pigmentosum, who also developed rickets. He was given one injection of vitamin D along with dietary vitamin D supplements to which he responded. He is being followed- up regularly in outdoor clinic with the advice to the parents to continue dietary vitamin D supplements and to avoid sun exposure.

Child, Preschool↗
PubMed2004

Perturbed homeostasis of peripheral T cells elicits decreased susceptibility to anti-CD3-induced apoptosis in prediabetic nonobese diabetic mice.

Activation-induced cell death (AICD) plays a key role in the homeostasis of the immune system. Autoreactive T cells are eliminated through AICD both from the thymus and periphery. In this study, we show that NOD peripheral T cells, especially CD8(+) T cells, display a decreased susceptibility to anti-CD3-induced AICD in vivo compared with T cells from diabetes-resistant B6, nonobese diabetes-resistant, and NOD.B6Idd4 mice. The susceptibility of NOD CD8(+) T cells to AICD varies in an age- and dose-dependent manner upon stimulation in vivo with either a mitogenic or nonmitogenic anti-CD3. NOD T cells preactivated by anti-CD3 in vivo are less susceptible than B6 T cells to TCR-induced AICD. Treatment of NOD mice with a mitogenic anti-CD3 depletes CD4(+)CD25(-)CD62L(+) but not CD4(+)CD25(+)CD62L(+) T cells, thereby resulting in an increase of the latter subset in the spleen. Treatment with a nonmitogenic anti-CD3 mAb delays the onset of T1D in 8.3 TCR transgenic NOD mice. These results demonstrate that the capacity of anti-CD3 to protect NOD mice from T1D correlates with its ability to perturb T cell homeostasis by inducing CD8(+) T cell AICD and increasing the number of CD4(+)CD25(+)CD62L(+) T cells in the periphery.

Aging↗
PubMed2004

Role of surfactant protein A in the innate host defense and autoimmunity.

Surfactant protein A (SP-A) is a lung collectin with diverse immunoregulatory activities. SP-A regulates the innate host defense by enhancing phagocytosis of pathogens and modulating the production of nitric oxide and cytokines by immune cells. Additionally, SP-A also modulates the phenotypic and functional properties of the cells of adaptive immune response such as dendritic cells (DCs) and lymphocytes. Bone marrow-derived DCs generated in the presence of SP-A fail to increase lipopolysaccharide-induced upregulation of major histocompatibility complex (MHC) class II and CD86 costimulatory molecule on DCs surface and behaves like "tolerogenic DCs". SP-A may also induce tolerance by suppressing the proliferation of activated T lymphocytes. Thus, based on immunoregulatory properties of SP-A, it may be employed as a therapeutic agent for the treatment of autoimmune disease and organ transplantation.

Animals↗
PubMed2004

Hyperresponsiveness, resistance to B-cell receptor-dependent activation-induced cell death, and accumulation of hyperactivated B-cells in islets is associated with the onset of insulitis but not type 1 diabetes.

B-cells proliferate after B-cell receptor (BCR) stimulation and are deleted by activation-induced cell death (AICD) during negative selection. We report that B-cells from type 1 diabetes-susceptible NOD and type 1 diabetes-resistant but insulitis-prone congenic NOD.B6Idd4B and NOR mice, relative to B-cells from nonautoimmune disease-prone C57BL/6 and BALB/c mice, display a hyperproliferative response to BCR stimulation and lower activation threshold in the absence or presence of interleukin 4 (IL-4). This hyperproliferation is associated with an increased proportion of NOD and NOR B-cells that enter into the S phase of the cell cycle and undergo cell division. The relative resistance to BCR-induced AICD of B-cells from NOD, NOR, and NOD.B6Idd4B mice, all of which develop insulitis, correlates with the presence of a higher percentage of hyperactivated B-cells in the spleen and islets of these mice than in nonautoimmune disease-prone C57BL/6 and BALB/c mice. The NOD islet-infiltrated activated B-cells are more responsive to further stimulation by IL-4 than activated spleen B-cells. Our results suggest that resistance to AICD and accumulation of hyperactivated B-cells in islets is associated with the onset of an inflammatory insulitis, but not type 1 diabetes.

Animals↗
PubMed2003

Surfactant protein A decreases nitric oxide production by macrophages in a tumor necrosis factor-alpha-dependent mechanism.

Surfactant protein A (SP-A) modulates the lung defense system through regulation of cytokines and nitric oxide (NO) production by alveolar macrophages (AMs). Whether SP-A upregulates or downregulates production of proinflammatory cytokines and NO is controversial. This study demonstrates the molecular mechanism(s) by which SP-A suppresses NO production by activated murine AMs. NO production by interferon-gamma (IFN-gamma) and IFN-gamma plus Mycobacterium avium-stimulated AMs was mediated through tumor necrosis factor-alpha (TNF-alpha) production, as addition of neutralizing anti-TNF-alpha antibodies during AMs stimulation resulted in reduced NO production. SP-A suppressed NO production by activated AMs by inhibiting TNF-alpha production. The maximum inhibitory effect of SP-A on NO production was observed at 20 microg/ml of SP-A concentration. Furthermore, SP-A inhibited activation of nuclear factor-kappa B, a transcription factor required for induction of TNF-alpha and inducible NO synthase genes. These findings suggest that SP-A suppresses NO production by activated AMs by inhibiting TNF-alpha secretion and nuclear factor-kappa B activation. This study also highlights the importance of SP-A levels in the lung, as changes in SP-A levels may modulate the local lung defense system.

Animals↗