Origin of CD4-CD8-B220+ T cells in MRL-lpr/lpr mice. Clues from a T cell receptor beta transgenic mouse.

Abnormal development of T cells in the thymus is thought to be related to autoimmune disease and the expansion of the unusual CD4-CD8-B220+ peripheral T cel subset that results in lymphadenopathy in MRL-lpr/lpr mice. Although we and others have previously shown that rearranged TCR-transgenes alter T cell development in the thymus and abrogate lymphoproliferative disease in lpr mice, the origin and developmental pathway of the LN CD4-CD8-B220+ T cells has not been fully elucidated. We therefore undertook the systematic analysis of the effect of a TCR-beta transgene on the production and differentiation of (lymph node) LN T cells and the production, differentiation, and release of thymocyte T cell populations.

Validation of a 20-minute steady-state jog as an estimate of peak oxygen uptake in adolescents.

Distance run tests are often used to estimate peak oxygen uptake (peak VO2) in children. This study examined the concurrent validity of a 20-min steady-state jog (20MSSJ). The sample consisted of 43 boys and 32 girls who performed a 20MSSJ and completed a maximal treadmill test 1 week later.

Prevalence of antibody to Helicobacter pylori in children in northern Nigeria.

Helicobacter pylori infection is common in northern Nigeria, but the age of acquisition is unknown. In a prospective study, immunoglobulin G antibodies to H. pylori were measured in 143 children under the age of 20 years.

A 'safe-site' for Salmonella typhimurium is within splenic polymorphonuclear cells.

Following oral or systemic infection with Salmonella typhimurium, the focus of infection is in the liver and spleen. The majority of Salmonella surviving in the liver and spleen by 4 h post infection are already in an environment where they are largely protected from subsequent killing. Previous studies have shown that the majority of surviving Salmonella are intracellular.

Genital secretory immune response to chronic simian immunodeficiency virus (SIV) infection: a comparison between intravenously and genitally inoculated rhesus macaques.

The humoral and genital secretory immune response to chronic SIV infection was compared between female Rhesus macaques inoculated by i.v. or intravaginal routes.

Properties of IgA-binding receptors on murine T cells: relative importance of Fc alpha R, beta-galactosyltransferase and anti-secretory component reactive proteins (ASCP).

Murine T cells and T-cell lines express receptors for the Fc of IgA (Fc alpha R); however, their molecular properties remain to be elucidated. In the present study, we examined three candidate molecules for IgA-binding receptors including Fc alpha R, beta-galactosyltransferase (beta-GT) and anti-secretory component (SC) reactive proteins (ASCP) expressed on T cells which might participate in the binding of different molecular forms of IgA. T-cell lines derived from CD4+ T cells of mouse Peyer's patches (PP) (designated PPT 4-6 and PPT 4-16) and from cloned PP T helper (Th) cell lines (ThHA1 #9 and #10) bound both monomeric and dimeric IgA (mIgA and dIgA), while the fusion partners (BW 5147 and R1.

Immunoregulatory functions for murine intraepithelial lymphocytes: gamma/delta T cell receptor-positive (TCR+) T cells abrogate oral tolerance, while alpha/beta TCR+ T cells provide B cell help.

Past work has shown that a subset of effector T cells with unique characteristics could abrogate hapten- or antigen-induced tolerance, and the reconstitution of this immune response has been termed contrasuppression. We have studied contrasuppression in a model of oral tolerance (OT) in which adoptively transferred antigen-specific T contrasuppressor (Tcs) cells reverse OT and result in antibody responses to the eliciting antigen. In the present study, we show that murine intraepithelial lymphocytes (IELs) from mice orally immunized with sheep red blood cells (SRBC) contain T cells that exhibit Tcs cell activity.

Spontaneously hypertensive rat: lymphoid depression is age dependent and mediated via a mononuclear cell subpopulation.

Immune dysfunction has been reported in spontaneously hypertensive rats (SHR), particularly in mature animals with established hypertension. The current study examined the time course of development of immune dysfunction and defined its cellular basis in male SHR and control normotensive Wistar-Kyoto rats (WKY). Mitogen-induced proliferative responses in lymphoid cells obtained from induced proliferative responses in lymphoid cells obtained from SHR thymus and spleen before (age 4 wk) and during the development of (ages 8 and 12 wk) hypertension and in age-matched normotensive WKY were monitored.

H. pylori, the most common bacterial infection in Africa: a random serological study.

This study was carried out to determine the prevalence of antibodies to Helicobacter pylori in northern Nigeria, a region with a low incidence of peptic ulceration. In a random, serological survey of 268 subjects, 228 (85%) of the population studied had IgG antibodies to H. pylori.

The mucosal immune system: from fundamental concepts to vaccine development.

Recent studies in experimental animals and humans have shown that the mucosal immune system, which is characterized by secretory IgA (S-IgA) antibodies as the major humoral defence factor, contains specialized lymphoid tissues where antigens are encountered from the environment, are taken up and induce B- and T-cell responses. This event is followed by an exodus of specific lymphocytes, which home to various effector sites such as the lamina propria regions and glands. These responses are regulated by T cells and cytokines and lead to plasma cell differentiation and subsequent production of S-IgA antibodies in external secretions.

Intestinal intraepithelial lymphocyte T cells are resistant to lpr gene-induced T cell abnormalities.

The mucosal immune system of the gastrointestinal (GI) tract consists of Peyer's patches (PP), which are IgA inductive sites, and more diffuse effector regions which include cells in the intraepithelial lymphocyte (IEL) compartment. Since autoimmune MRL lpr/lpr (MRL/lpr) mice develop a proliferating CD3+, CD4-, CD8- (double negative; DN), B220+ T cell subset in systemic lymphoid tissue, we have initiated studies to determine the distribution of CD3+, DN, B220+ T cells (B220+ T cells or lpr/lpr T cells) in the GI immune system. Specifically, we examined T cell subsets separated according to expression of CD4, CD8, Thy-1, B220, alpha/beta T cell receptor (TcR) and gamma/delta TcR in PP and IEL of MRL/lpr mice at 6, 12 and 21 weeks of age.

Isolation and functional comparison of Dmyd, the Drosophila homologue of the vertebrate myogenic determination genes, with CMD1.

We have isolated a cDNA clone, called Dmyd for Drosophila myogenic determination gene, from a 0-16 hour Drosophila embryo library that encodes a protein with structural and functional characteristics similar to the members of the vertebrate MyoD family (Paterson et al 1991). Dmyd encodes a polypeptide of 332 amino acids with 82% identity to MyoD in the 41 amino acids of the putative helix-loop-helix region and 100% identity in the 13 amino acids of the basic domain proposed to contain the essential recognition code for muscle specific gene activation. The gene is unique and maps to 95A/B on the right arm of the third chromosome.

Transforming growth factor-beta enhances secretory component and major histocompatibility complex class I antigen expression on rat IEC-6 intestinal epithelial cells.

Transforming growth factor-beta (TGF-beta) has been implicated as having a role in inflammatory responses by inducing cellular infiltration and the release of inflammatory cytokines. In this study, the IEC-6 rat intestinal epithelial cell line was used as a model to assess the effect of TGF-beta 1 on the expression of various plasma membrane determinants. TGF-beta 1 induced a dose-dependent increase in the percentage of cells expressing surface secretory component (SC) and class I major histocompatibility (MHC) antigens.

Effects of delta-9-tetrahydrocannabinol exposure on adrenal medullary function: evidence of an acute effect and development of tolerance in chronic treatments.

Previous studies have shown that the secretion of several stress-related hormones can be altered by exposure to marihuana or its purified constituents. The purpose of this study was to examine changes in adrenal medullary function caused by acute, subchronic and chronic treatments with two different doses of delta-9-tetrahydrocannabinol (THC). Acute exposure to THC caused a significant decrease in the adrenal medulla contents of both norepinephrine (NE) and epinephrine (E) and a significant increase in the E/NE ratio.

Problems with substantial limb lengthening.

Limb lengthening takes careful planning and meticulous outpatient care and still is burdened by minor complications. Experience may lessen major complications, but pin tract problems, swelling, and pain will plague these patients. A large group of patients can benefit from lengthening procedures, and new techniques are improving the risk-benefit balance.

Biodegradable and biocompatible poly(DL-lactide-co-glycolide) microspheres as an adjuvant for staphylococcal enterotoxin B toxoid which enhances the level of toxin-neutralizing antibodies.

Microspheres composed of biocompatible, biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) and staphylococcal enterotoxin B (SEB) toxoid were evaluated as a vaccine delivery system when subcutaneously injected into mice. As measured by circulating immunoglobulin G (IgG) antitoxin titers, the delivery of SEB toxoid via DL-PLG microspheres, 1 to 10 microns in diameter, induced an immune response which was approximately 500 times that seen with nonencapsulated toxoid. The kinetics, magnitude, and duration of the antitoxin response induced with microencapsulated toxoid were similar to those obtained when an equal toxoid dose was administered as an emulsion with complete Freund adjuvant.

Targeting and controlled release of antigens for the effective induction of secretory antibody responses.

Increased awareness of the fact that the mucosal membranes are the portals of entry for the majority of infectious agents, and that antibodies in external secretions often correlate better with protection than do corresponding antibodies in serum, has prompted many recent studies aimed at the selective induction of antibodies in mucosal secretions. The recent development of novel technologies (expression of antigens in various microbial vectors that colonize mucosal surfaces and incorporation of antigens in biodegradable microspheres) indicate that the goal of vaccination with enhanced induction of both mucosal and systemic immune responses is attainable.

Regulation of mucosal responses by CD4+ T lymphocytes: effects of anti-L3T4 treatment on the gastrointestinal immune system.

The role of CD4+ T cells in the gastrointestinal (GI) immune system in vivo was studied in mice selectively depleted of this subset by treatment with monoclonal anti-L3T4 (GK1.5) mAb. Treatment of young BALB/c mice with weekly injections of anti-L3T4 mAb resulted in a selective depletion of CD4+ T cells in both IgA effector (lamina propria regions of the intestine; LP) and inductive (Peyer's patch; PP) sites.

Abnormal thymocyte development and production of autoreactive T cells in T cell receptor transgenic autoimmune mice.

Development of a C57BL/6-+/+ TCR transgenic mouse containing the rearranged TCR alpha- and beta-chain specific for the Db + HY male Ag results in production of a nearly monoclonal population of early thymocytes expressing the Db + HY reactive TCR. These thymocytes are autoreactive in H-2Db male mice and undergo clonal deletion and down-regulation of CD8. To study the effect of the lpr gene on development of autoreactive T cells, these transgenic mice were backcrossed with C57BL/6-lpr/lpr mice.