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J G Tew

Publications and source records attributed to J G Tew.

At least 55 records · Page 3Linked to original sources
PubMed1996

Genetic segregation analyses of serum IgG2 levels.

Summary : The aim of this study was to determine whether there was evidence for a genetic component in the immune response as measured by IgG2 levels. The study was motivated by our studies of early-onset periodontitis (EOP), a group of disorders characterized by rapid destruction of the supporting tissues of the teeth in otherwise healthy individuals. EOP has two subforms, localized juvenile periodontitis (LJP) and a generalized form (G-EOP). IgG2 levels are elevated in LJP but not G-EOP individuals; and African-American IgG2 levels are higher than Caucasian levels regardless of EOP status. IgG2 levels were determined in 123 EOP families and in 508 unrelated non-EOP control individuals. Segregation analysis under the regressive model approach of Bonney was used to analyze IgG2 levels for evidence of major locus segregation. After adjusting for LJP status, race, sex, and age, the best fitting model was an autosomal codominant major locus model (accounting for approximately 62% of the variance in IgG2), plus residual parent/offspring and spousal correlations. Smoking and GM23 are also known to affect IgG2 levels. If additional adjustments are made for smoking and GM23, the best-fitting model is still a codominant major locus but with no significant residual correlations.

Black People↗
PubMed1996

GM allotypes and IgG subclass concentrations in blacks.

IgG subclass concentrations were measured in 352 black Americans. Sera were also typed for nine GM allotypes. Serum concentrations of IgG1, IgG3, and IgG4 varied, to different degrees, according to GM phenotypes. The concentration of IgG1 was lower in subjects with GM 1,3,17 5,6,13 compared to those who lacked this phenotype. Elevated levels of IgG3 and IgG4 were associated with GM 1,17 5,6,13 and GM 1,3,17 23 5,13, respectively. Subjects with GM 1,17 5,13,21 had lower levels of IgG3 than individuals with other phenotypes. IgG2 levels were not associated with any of the GM phenotypes. To our knowledge, this represents the first report of an association between GM allotypes and IgG subclasses in blacks.

Black People↗
PubMed1995

Follicular dendritic cells and human immunodeficiency virus infectivity.

Large amounts of human immunodeficiency virus (HIV) localize on follicular dendritic cells (FDC) in the follicles of secondary lymphoid tissues following viral infection. During clinical latency, active viral infection occurs primarily at these sites. As HIV on FDC is in the form of immune complexes, some of which may be formed with neutralizing antibody, we investigated whether HIV on FDC is infectious. We report here that HIV on FDC is highly infectious. Furthermore, FDC can convert neutralized HIV into an infectious form even in the presence of a vast excess of neutralizing antibody. Thus FDC may provide a mechanism whereby HIV infection can continue in the presence of neutralizing antibody.

Animals↗
PubMed1995

Follicular dendritic cells and B cell chemotaxis.

B cells isolated from germinal centers (GC) of immune mice 2-5 days after antigen (Ag) challenge migrate in response to chemotactic signals, whereas GC B cells isolated at other times and resting B cells do not. Since B cells are in direct contact with follicular dendritic cells (FDC) in GC we reasoned that FDC might play a role in enabling B cells to become chemotactically active. Resting B cells were co-cultured with FDC either with or without anti-mu-dextran (anti-mu-dex) as an Ag surrogate and/or recombinant interleukin (rIL)-4 as a T cell surrogate. After 3 days, the B cells were isolated and their migration to chemotactic factors contained in zymosan-activated serum assessed in microchemotaxis chambers. B cells incubated alone or with anti-mu-dex or rIL-4 showed minimal migration, which could be increased if both anti-mu-dex or rIL-4 were present. However, maximal migration was obtained when B cells were cultured with FDC, and this was not increased by addition of anti-mu-dex and/or rIL-4, indicating that the FDC signal was a primary signal and did not require pre-activation of the B cells. Checkerboard analysis using variation in concentration and location of the chemoattractant in chemotaxis chambers indicated that both chemotaxis and chemokinesis occurred. B cell migration began within 6 h of culture, peaked by 48 h and decreased thereafter. Removal of FDC or interference with FDC-B cell contact ablated or significantly decreased induction of B cell migration. Furthermore, induction did not require functional T cells. These data indicate that FDC can induce resting B cells to become responsive to chemotactic signals.

Animals↗
PubMed1995

Follicular dendritic cells and the maintenance of IgE responses.

Antigen (Ag) is retained for long periods of time in secondary lymphoid tissues in the form of immune complexes on follicular dendritic cells (FDC). Ag retained on FDC is thought to play a role in maintaining antibody (Ab) responses in vivo. A model for study of Ab production induced by retained Ag in vitro is the spontaneous Ab response. In this response, specific Ab production is induced spontaneously (no exogenous Ag needed) in cultures derived from secondary lymphoid tissues containing persisting Ag. Specific IgG is spontaneously induced and we reasoned that FDC may also play a role in the maintenance of specific IgE responses. To test this hypothesis, we monitored spontaneous anti-ovalbmin (OVA) IgE production in cultures of lymph node (LN) fragments from OVA-immunized mice. In addition, highly enriched preparations of OVA bearing FDC were added to OVA-specific memory cells in an attempt to stimulate OVA-specific IgE production. Months after secondary immunization, anti-OVA IgE responses were spontaneously induced when fragments from draining LN were placed into culture. Furthermore, FDC bearing OVA from draining LN induced anti-OVA IgE production when incubated with spleen cells from OVA-immune mice whereas identical cultures with FDC bearing environmental Ag from non-draining LN of the OVA immune animals did not. The anti-OVA IgE responses were elicited only in cultures containing OVA-immune memory cells indicating that specific memory cells were critical for these anti-OVA IgE responses. Removal of FDC from cultures with an FDC-specific mAb dramatically decreased anti-OVA IgE production. These studies demonstrate that FDC can induce specific memory T and B cells to produce IgE and help support the concept that FDC-associated antigen may be involved in the long-term maintenance of specific IgE responses.

Animals↗
PubMed1995

Expression of the intercellular adhesion molecule-1 on high endothelial venules and on non-lymphoid antigen handling cells: interdigitating cells, antigen transporting cells and follicular dendritic cells.

Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the development of germinal center reactions in vitro, and the present study was undertaken to determine the distribution of ICAM-1 in active germinal centers in vivo and in murine secondary lymphoid tissues in general. Anti-ICAM-1-specific monoclonal antibodies were used in conjunction with immunohistochemistry at both the light and ultrastructural levels of resolution. Examination of cryostat sections of lymph nodes, spleens, and Peyer's patches revealed that anti-ICAM-1 distinctly labeled cells in the light zones of germinal centers, a few cells in the T cell zones (e.g. paracortex of lymph nodes), cells in the sinus floor of the subcapsular sinuses of lymph nodes, and high endothelial venules (HEV). Ultrastructural studies revealed that the cells labeling with anti-ICAM-1 in germinal centers were follicular dendritic cells (FDC) which appeared to have more ICAM-1 than any other cell type. The surfaces of well-developed, intricate, convoluted FDC processes were intensely labeled even under conditions where B cells appeared negative. Interdigitating cells (IDC) were also labeled as were certain endothelial cells in the HEV. The cells in the subcapsular sinus floor labeling with anti-ICAM-1 were the "antigen transporting cells" (ATC) that carry antigen-antibody complexes into lymph node follicles. We suspect ATC are FDC precursors which mature into FDC in the follicles. Interestingly, FDC, IDC, and ATC are 3 important accessory cells known to handle antigens in specific compartments of lymphoid tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Smoking and its effects on early-onset periodontitis.

The findings of a recent study show that smoking was more prevalent in a group of patients with generalized early-onset periodontitis and adult periodontitis than in patients with localized juvenile periodontitis or healthy periodontium. In patients with generalized early-onset periodontitis, smoking had a significant effect on periodontal attachment loss; these patients had significantly more teeth with affected sites and a greater mean loss of attachment than patients who did not smoke. Thus, the risk of smoking could greatly accelerate tooth loss in this relatively young group of individuals who are already at high risk for progressive periodontal attachment loss.

Adolescent↗
PubMed1995

Loss of follicular dendritic cells in murine-acquired immunodeficiency syndrome.

BACKGROUND: The disease caused by HIV-1 leads to the destruction of follicular dendritic cells (FDC) and the follicular architecture in secondary lymphoid tissues. The murine acquired immunodeficiency syndrome (MAIDS, caused by LP-BM5) serves as an animal model for study of mechanisms involved in development of retrovirus-induced immunodeficiencies. The present study was undertaken to determine whether LP-BM5 infection leads to the destruction of murine FDC and the normal follicular architecture in secondary lymphoid tissues. EXPERIMENTAL DESIGN: Mice were infected with LP-BM5, and the follicular architecture and FDC networks were assessed. The pathologic changes observed were correlated with FDC function. RESULTS: Three weeks after infection, FDC networks were present, and they often appeared hyperplastic. However, by 1 month after infection, distorted lymphoid follicles were apparent, and the intensity of FDC labeling began to decline. FDC disappeared first in the spleen, and in hyperimmunized mice, FDC in draining lymph nodes disappeared before FDC in nondraining lymph nodes. By 4 months, the normal follicular localization of B cells was missing, and FDC were not detectable in most tissues. As the FDC and the normal lymphoid architecture degenerated, extrafollicular foci of immunoblasts and plasma cells appeared in areas typically reserved for T cells, and the Thy 1.2+ T cells were dispersed. Of interest, the total number of Ig-producing cells increased as the disease progressed; in contrast, the number of anti-human serum albumin-producing cells in mice immunized with human serum albumin before infection decreased. CONCLUSIONS: These data indicate that, like HIV-1 infection, LP-BM5 infection leads to the loss of FDC and the normal follicular architecture. However, morphologic changes were not observed until after FDC had lost their normal ability to trap and retain Ag. These data indicate that retroviral infections may cause FDC dysfunctions long before FDC are destroyed.

Animals↗
PubMed1994

Serum immunoglobulin G subclass concentrations in periodontally healthy and diseased individuals.

Patients with localized juvenile periodontitis (LJP) often have high titers of antibody reactive with the serotype-specific immunodominant carbohydrate antigen of Actinobacillus actinomycetemcomitans serotype b. The vast majority of this A. actinomycetemcomitans serotype b-specific antibody is immunoglobulin G2 (IgG2). The present study was undertaken to determine whether the overall total levels of IgG2 in the sera of LJP patients are elevated. LJP patients and nonperiodontitis (NP) controls matched for age, race (black and white), and gender were studied. Additional controls included patients with adult periodontitis (AP) and patients similar in age to LJP patients but with the more-severe, generalized form of early-onset periodontitis (SP). Sera from over 700 periodontally characterized subjects were examined by using radial immunodiffusion to quantitate IgG2 as well as IgG1, -3, and -4, which were included for comparison. Serum IgG2 levels increased with age, and this was most dramatic around puberty. Black subjects in all periodontal groups had nearly 1 mg more IgG2 per ml than their white counterparts. Serum IgG2 levels were elevated (about 30 to 40%) in LJP patients of both races compared with their age- and race-matched NP controls (P < 0.01). In contrast, SP patients and AP patients had IgG2 levels comparable to their age- and race-matched NP controls. No other IgG subclass concentration correlated with periodontal diagnosis except for IgG3, which was elevated in white LJP patients. We reason that the high levels of serum IgG2 in LJP may be helpful in localizing periodontal destruction.

Adult↗
PubMed1994

Follicular dendritic cell function and murine AIDS.

Infection of mice with LP-BM5 elicits an immunodeficiency state referred to as murine acquired immune deficiency syndrome (MAIDS). Shortly after infection, retrovirus particles become associated with follicular dendritic cells (FDC) and this study was undertaken to determine whether retroviruses alter FDC functions. The FDC functions examined included the ability to: (1) retain antigen (Ag) trapped prior to infection; (2) trap new Ag after infection; (3) maintain specific IgG responses; and (4) provide co-stimulatory signals to B cells. Mice were infected with LP-BM5 and the ability of their FDC to trap and retain 125I-Ag (HSA) was assessed. Serum anti-HSA levels were monitored and FDC co-stimulatory activity was indicated by increased B-cell proliferation. HSA trapped on FDC prior to infection began to disappear by 3 weeks and was practically gone by 6 weeks. Serum anti-HSA titres were maintained normally for about 3 weeks after infection and then declined precipitously. The ability of FDC to trap new Ag began to disappear around the second and third week of infection and was markedly depressed by the fourth week. However, FDC recovered from infected mice retained their ability to co-stimulate anti-mu- and interleukin-4 (IL-4)-activated B cells throughout a 5-week period. In short, the ability of FDC to trap and retain specific Ag and maintain specific antibody levels was markedly depressed after retrovirus infection. However, FDC from infected mice continued to provide co-stimulatory signals and these signals may contribute to the lymphadenopathy and splenomegaly characteristic of MAIDS.

Animals↗
PubMed1993

Induction of functional follicular dendritic cell development in severe combined immunodeficiency mice. Influence of B and T cells.

Ag injected into immune mice immediately complexes with specific antibody. Immune complexes not phagocytosed by macrophages are transported by Ag transport cells to lymph node follicles for trapping by follicular dendritic cells (FDC). These FDC serve as a long term repository of unprocessed Ag that is believed to maintain both B cell memory and the secondary antibody response. Severe combined immunodeficiency mice lack functional B cells and T cells. Consequently, this mutation also appears to affect the ability to produce Ag-retaining FDC. to assess B and T cell requirements for FDC development and function, severe combined immunodeficiency mice were reconstituted with BM, or mature B and T cells. The development of a FDC reticulum, a three-dimensional network produced by the intertwining of FDC dendrites was assessed by Ag trapping on FDC using the histochemically detectable Ag horseradish peroxidase and quantitated by morphometry. The results showed that bone marrow transplants or B and T cells transferred together supply the required elements for the development of severe combined immunodeficiency FDC reticula that function in Ag trapping and the induction of the germinal center. In contrast, B cells or T cells injected separately induced a minimal development of FDC reticulum. The B and T cell requirements demonstrated here strongly indicate that B-T cell collaboration and the factors these cells produce are essential for FDC development.

Animals↗