Biomedical subjects

H Renz

Publications and source records attributed to H Renz.

At least 127 records · Page 7Linked to original sources

PubMed1995

The central rôle of T-cells in allergic sensitization and IgE regulation.

The atopic phenotype develops on the basis of a genetic predisposition. Several candidate genes and chromosomal regions have been recently identified that may play a rôle in the development of allergic sensitization and total IgE production, including genes encoding MHC and T-cell receptor (TCR) molecules, cytokines and others. Genetic predisposition triggers and immunological dysregulation which is controlled by CD4+ T-cells. (Specialized) antigen presenting cells process and present allergenic peptides (T-cell epitopes) on MHC class II molecules to T-cells that recognize MHC plus peptide using the TCR. Cognate and non-cognate interaction results in T-cell activation. Selective stimulation of the allergen specific T-cells is the result of allergen-specific sensitization. These T-cells are characterized by (simultaneous) production of IL-3, IL-4, IL-5 (and may be IL-13). These cytokines control the production of IgE by B cells and play a critical rôle in the activation and differentiation of effector cells of the allergic response (such as eosinophils and mast cells). In addition to MHC-TCR interaction and cytokine production, ligation of CD40 and CD40L represents an additional requirement for the production of functional IgE molecules. Immediate hypersensitivity responses are characterized by an early phase response (triggered by many mediators released from effector cells following allergen exposure, IgE cross-linking and activation of signal transduction pathways) and a late phase response that is mediated to a large extend by the influx of T-cells and effector cells into the site of allergic inflammation. Deliniation of the immunological mechanisms that result in allergic sensitization will contribute to the development of specific immunomodulatory strategies aimed to prevent the development of allergies.

Animals↗

PubMed1995

Inhibition of allergen-induced IgE and IgG1 production by soluble IL-4 receptor.

In this study, the effect of soluble IL-4 receptors (sIL-4R) on murine allergen-induced IgE and IgG1 production was examined. Lymphocytes from mice sensitized to the allergens ragweed (RW) or ovalbumin (OVA) in vivo were restimulated in vitro with the sensitizing allergen in the presence of either a soluble murine sIL-4R, a dimeric sIL-4R Ig fusion protein (sIL-4R/Fc), or anti-IL-4 antibody in 14-day cultures. Both monomeric and dimeric sIL-4R inhibited polyclonal IgE (approximately 70%) and IgG1 (approximately 35%) production in a dose-dependent fashion, similar to that observed in the presence of the anti-IL-4 antibody. Allergen-specific IgE and IgG1 were inhibited to a greater degree. Addition of sIL-4R was most effective when present in the culture during the first 3 days and added not later than day 6. In kinetic experiments, we distinguished ongoing IgE production from precommitted B cells versus newly induced IgE synthesis and found that newly induced IgE production was the major target of the sIL-4Rs. These data demonstrate the efficacy of sIL-4R in inhibiting the early stages of the IgE B-cell maturation pathway and indicate the potential of sIL-4R for the inhibition of IgE production in vivo.

Animals↗

PubMed1995

Therapeutic interference with interferon-gamma (IFN-gamma) and soluble IL-4 receptor (sIL-4R) in allergic diseases.

Allergic sensitization is controlled by CD4+ T cells. A complex interaction between antigen-presenting cells, T- and B-cells results in the production of (allergen) specific IgE. Analysis of the lymphokine profile of lymphocytes from patients with bronchialasthma and atopic dermatitis revealed an imbalance in cytokine production. An enhanced production of IL-4 was accompanied by low or absent amounts of IFN-gamma. Since both cytokines play a central role in the regulation of IgE, it was examined whether therapeutic interference on the level of cytokine production may provide an useful tool to alter lymphocyte functions in allergic diseases. Two different model systems were employed to study the effects of soluble IL-4R (sIL-4R) under in vitro and in vivo conditions. (1) A mouse model system for allergic sensitization and increased airways responsiveness (AR) was employed to examine whether in vivo treatment with recombinant murine sIL-4R may prevent the development of allergic sensitization. It was found that local treatment through the airways and the lung as carried out by aersolization of the receptor offered a route of application that prevented the development of allergen-induced and allergen-dependent immediate hypersensitivity responses including the development of increased AR. (2). The in vitro effects of humans sIL-4R on functions of mononuclear cells prepared from two patients with most severe atopic dermatitis were examined. Incubation of lymphocytes with allergens in the presence and absence of sIL-4R indicated that the soluble receptor suppressed allergen-induced lymphocyte proliferation and allergen-dependent IgE, IgG and IgM production. In addition a complete suppression of allergen-specific IgE production was detected in the presence of sIL-4R. These data suggest that sIL-4R may provide a useful drug to modify lymphocyte-dependent immune functions in allergic diseases.

Allergens↗

PubMed1994

Cellular DNA content and survival in advanced ovarian carcinoma.

BACKGROUND: The prognosis of patients with advanced ovarian cancer is generally poor. To date, no satisfactory methods for predicting individual prognosis have been reported, especially in patients with little or no residual tumor after debulking. METHODS: The authors investigated in a retrospective study the prognostic significance of nuclear DNA content as measured by flow cytometry of the tumor specimens from 184 women with nonpretreated International Federation of Gynecology and Obstetrics Stage III and IV ovarian cancer. Clearly defined inclusion criteria for the study population were used. RESULTS: Seventy-one (39%) cancers were diploid, whereas 113 (61%) were aneuploid. Ploidy showed a significant correlation with clinical and morphologic features such as age, histologic grade, serous histologic type, and residual tumor after debulking. No significant correlation was found between ploidy and ascites, estrogen- and progesterone receptor levels, and elevated pretreatment CA-125 levels. Univariate analysis showed significant correlations between overall survival and histologic grade (P = 0.003), patient age (P = 0.001), residual tumor after primary surgery (P < 0.001), stage (P = 0.019) and ploidy (P = 0.009). Multivariate analysis revealed residual tumor (P < 0.001) and age (P = 0.051) to be associated independently with survival. Ploidy was not established as an independent prognostic factor. CONCLUSIONS: These results suggest that abnormalities of the nuclear DNA content in advanced ovarian carcinomas are associated with various clinical and morphologic prognosticators, but that ploidy is not an independent prognostic factor for survival.

Adult↗

PubMed1994

Differential activation of p21ras in CD45RA+ and CD45RO+ human T lymphocytes.

CD45RA+ and CD45RO+ human T cells differ in their functional responses to different forms of mitogenic stimulation. However, little is known about the intracellular signaling events related to the functional differences in these two subsets. In the present study, we examined the ability of different Abs to the TCR/CD3 complex to activate the p21ras proto-oncogene product in CD45RA+ and CD45RO+ T cells. Stimulation with soluble OKT3 anti-CD3 mAb induced activation of p21ras in CD45RA+ cells but not in CD45RO+ cells, although soluble anti-CD3 was able to induce both activation of CD3-associated kinases and IL-2 responsiveness in CD45RO+ cells. Similar results were obtained by using UCHT1, a different anti-CD3 Ab. In contrast, cross-linked anti-CD3 or the combination of phorbol ester and ionomycin were found to activate p21ras equally in both T cell subsets. Our results demonstrate a selective inability of CD45RO+ human T cells to activate p21ras in response to soluble anti-CD3 mAb.

Antibodies, Monoclonal↗

PubMed1994

Nebulized but not parenteral IFN-gamma decreases IgE production and normalizes airways function in a murine model of allergen sensitization.

An animal model of local allergen (airways) sensitization was employed to study the effects of rIFN-gamma administered by ultrasonic nebulization through the airways on IgE production and airways responsiveness. BALB/c mice exposed to aerosolized OVA daily for 10 days developed a predominant anti-OVA IgE response, immediate cutaneous reactivity to OVA, and increased airways responsiveness (AR). Mice were treated with rIFN-gamma, either systemically or locally via the airways, following different protocols; i.p. rIFN-gamma failed to modulate the course of OVA sensitization, although total IgE levels in the serum were decreased by 50%. Anti-OVA IgE levels remained elevated, immediate skin test responses to OVA persisted, and AR was increased. However, local treatment of the airways with nebulized rIFN-gamma caused a 66% decrease in serum anti-OVA IgE and a twofold rise in IgG2a levels. Cutaneous reactivity to OVA was reduced and AR was also normalized after nebulized rIFN-gamma. In contrast to the i.p. route, treatment with nebulized rIFN-gamma resulted in a reduction in the in vitro IgE production by lymphocytes in response to OVA and IL-4. The timing of treatment with nebulized rIFN-gamma was important in determining the immunomodulatory response. Treatment after day 7 of OVA exposure failed to modulate sensitization. Treatment regimens with nebulized rIFN-gamma that began before day 7 of OVA exposure were able to decrease anti-OVA IgE. Only treatment regimens that included 3 days of nebulized IFN-gamma before OVA sensitization caused a decrease in cutaneous reactivity and normalization of AR. The data demonstrate that both the route and timing of rIFN-gamma administration are critical factors in the immunomodulation of the immediate allergic response to allergen sensitization via the airways.

Aerosols↗

PubMed1994

Inhibition of IgE production and normalization of airways responsiveness by sensitized CD8 T cells in a mouse model of allergen-induced sensitization.

The functional role of CD8 T cells in in vivo IgE production, immediate cutaneous reactivity, and altered airways responsiveness (AR) was examined in a murine model of allergen-induced sensitization. Exposure of BALB/c mice to nebulized OVA triggered an IgE anti-OVA response in the serum, immediate-type skin test responses to OVA, and the development of increased AR (as measured by nonspecific reactivity to electrical field stimulation). In spleens of sensitized mice, analysis of the distribution of CD4/CD8 T cell subpopulations revealed an increase in total numbers of CD8 T cells. Transfer of purified spleen CD8 T cells from OVA-sensitized mice (CD8OVA) to sensitized recipients reduced serum IgE anti-OVA production by roughly 50%. Furthermore, studies of in vitro Ig production indicated that mononuclear cells from recipients of CD8 cells (CD8OVA > CD8PBS) produced less IgE and IgG1 antibodies, whereas in vitro IgG2a production was enhanced. The suppression of IgE production in recipients of CD8OVA T cells was associated with the failure to respond to intradermal challenge with OVA. The increase in AR found in sensitized mice was prevented after transfer of CD8OVA cells. When CD8 T cells from nonimmunized animals (CD8PBS) were used for the transfer into sensitized recipients, serum anti-OVA IgE was decreased by only 20%, whereas skin test reactivity and AR were not significantly affected. The ex vivo analysis of the pattern of cytokine-producing lymphocytes by immunofluorescence microscopy indicated that the sensitization procedure increased the fraction of IFN-gamma- and IL-4-positive cells in the spleen. Further in vitro analysis demonstrated that a high percentage of CD8 T cells were positive for IFN-gamma, whereas IL-4 was produced mainly by CD4 T cells. These data suggest that CD8 T cells may play an important role in the negative regulation of IgE production and AR and that IFN-gamma may be a relevant mediator of the functions of CD8 T cells in this model.

Animals↗

PubMed1994

Inhibition of the development of immediate hypersensitivity by staphylococcal enterotoxin B.

We investigated the ability of staphylococcal enterotoxin B (SEB) to modify the immediate hypersensitivity response induced in BALB/c mice following sensitization to ovalbumin (OVA), a response mediated by OVA-reactive V beta 8 T cells. Mice were sensitized by skin painting with OVA every second day over a period of 2 weeks. SEB, a potent activator of V beta 8+ T cells, was administered at the same site where OVA was applied (skin of the lower abdomen) following two different protocols. In protocol (A) SEB was injected intradermally 1 day before painting with OVA and on day 7; in protocol B, SEB was injected each time OVA was applied to the skin (eight times). SEB (but not SEA) altered the development of immediate hypersensitivity to OVA, as demonstrated by the reduction in allergen-specific IgE, decreased OVA-specific immediate skin test responsiveness, and prevented the development of increased airways responsiveness after bronchial challenge with OVA. Injections of SEB did not alter the proliferative responses of local draining lymph node cells or spleen mononuclear cells to OVA, indicating that administration of SEB did not inhibit the sensitization of OVA, but shifted the immune response away from an immediate type response (IgE/IgG1) to IgG2a, IgG2b and IgG3. Although both protocols of SEB treatment did not lead to a major deletion of the V beta 8 T cell population, they did reduce the proliferative response of V beta 8+ T cells to OVA. These data indicate that the bacterial toxin SEB is capable of modifying the immediate hypersensitivity response induced by OVA by altering the functional capacity of antigen-reactive V beta 8 T cells.

Allergens↗

PubMed1994

Regulation of B-cell immune responses: predominant role of interleukin-4 in triggering cell proliferation and Ig production in competent B cells.

We established a system for induction of competence in B cells following brief (45 min) exposure to either the combination of phorbol 12,13-dibutyrate (PDB) and ionomycin (I) (PDB/I) or PDB/anti-IgM. B cells, rendered competent in this fashion, were able to respond to PDB in the second or progression phase of culture but did not proliferate on their own. In addition, competent B cells were IL-2- or IL-4-responsive, due to up-regulation of their respective receptors following competence induction. IL-4 was found to have the most effective role in the progression phase to promote DNA synthesis and was able to enhance both IL-2 and IL-4 receptor expression. Whereas provision of IL-4 could induce IgM, IgG, and IgA in the absence of T cells, it did not result in IgE production. IgE production was only achieved in the presence of activated T cells (competent) together with competent B cells. These results indicate that IL-4 has a major role in B-cell immune responses following initial activation and trigger the cells, in the absence of T cells or other factors, to proliferate and differentiate into Ig-secreting cells. For IgE production in competent B cells, however, IL-4 alone could not overcome the requirement for activated T cells.

Antibodies, Anti-Idiotypic↗

PubMed1994

Isolation and characterization of human antigen-specific B lymphocytes.

Antigen-specific B cells from the peripheral blood of immunized donors were isolated following rosette formation with antigen-coated immunomagnetic beads and were phenotypically and functionally characterized. B cells separated with tetanus toxin (TT)- or keyhole limpet hemocyanin (KLH)-coated beads produced significant amounts of specific IgM and IgG antibodies when they were transformed with Epstein-Barr virus or cultured with autologous T cells in the presence of a specific antigen. Cells isolated from peripheral blood mononuclear cells (PBMC) with TT-coated beads consisted mostly of B cells (88.7% CD20+). B cells detected among the rosetting cells were predominantly sIgM+ with low percentages of the other isotype-expressing B cells. The mean percentage of TT-specific B cells among adult donors was 0.34% of PBMC, and increased to up to 2% following a booster immunization with antigen. A similar increase in the number of rosetting B cells was also observed following in vitro culture of PBMC with antigen. These findings demonstrate that immunomagnetic bead selection serves as a specific and reliable approach in identifying and isolating antigen-specific B cells from human PBMC and provides a valuable method for studying T-B interactions in antigen-specific immune responses.

Adult↗

PubMed1994

Suppression of cytokine-dependent human T-cell proliferation by intravenous immunoglobulin.

Human intravenous immunoglobulin (hIVIG) modifies the course of numerous immune-mediated diseases, but its specific mode of action remains unknown. In order to delineate possible immunoregulatory mechanisms, we studied the effects of hIVIG on the in vitro proliferation of human T cells. Cells from normal donors were stimulated with anti-CD3 antibody, tetanus toxoid antigen or the combination of a phorbol ester/ionomycin (P/I) and incubated with increasing concentrations of hIVIG (1 mg/ml to 10 mg/ml) for three to seven days. Addition of hIVIG inhibited anti-CD3 and tetanus but not P/I-induced proliferation in a dose-dependent manner. Addition of exogenous IL-2 to the cultures overcame the inhibitory effect of hIVIG; addition of IL-4 was ineffective. To further define the effect of hIVIG on specific cell populations, competent, purified T cells were stimulated with anti-CD3 or phorbol ester for three days in the presence of hIVIG. Addition of hIVIG blocked anti-CD3 and phorbol ester-induced stimulation of competent T cells. In cultures of competent T cells, either IL-2 or IL-4 was successful in reversing the hIVIG-induced inhibition. In these cultures, hIVIG also significantly prevented the synthesis/secretion of both IL-2 and IL-4 in PDB-stimulated competent T cells. Taken together, these data suggest that one mechanism of action of hIVIG may be through its interference with cytokine-dependent T-cell proliferation.

Cell Division↗

PubMed1994

[Morphometric studies on the fetal development of the human mandible].

Serial sections of eleven human mandibles of embryos and fetuses ranging in size from 18 mm CRL to 66 mm CRL were computer-graphically reconstructed. The extension of the Meckel cartilage and the mandibular bony structures were morphometrically studied. In emphasis the study encompassed measurements portraying length, width, dorsal opening angle, and the position of the mental foramen. In addition five mandibles of human embryos and fetuses with a size range between 30 and 50 mm CRL were radiographically examined. Results showed that in the younger specimens between 21 and 29 CRL size development of the structures of the mandible and the development of overall fetal body size take place independently from each other. During further development a change in the form of the mandible from a wide V over an acute V to a more rounded U form was observed.

Cartilage↗

PubMed1994

Enhancement of IgE production by anti-CD40 antibody in atopic dermatitis.

It has been recently recognized that the obligate requirement for T cells in the development of IgE responses can be substituted for by anti-CD40 antibody. In this study of patients with atopic dermatitis and high IgE levels, we have analyzed the role of the CD40 molecule in IgE production. Costimulation of peripheral blood mononuclear cells (PBMCs) from normal donors with interleukin-4 (IL-4) and anti-CD40 monoclonal antibody resulted in a selective increase in IgE production; either reagent alone, however, was ineffective. In contrast, addition of anti-CD40 monoclonal antibody alone to PBMCs or B cells from patients with atopic dermatitis markedly increased IgE production, even in the absence of exogenous IL-4. With the use of an ELISA spot assay, this increase in IgE production was attributed to an expansion of IgE-secreting B cells. In anti-IgM-stimulated lymphocyte cultures from patients with atopic dermatitis the costimulation with anti-CD40 induced strong lymphocyte proliferation. Similar results were observed with anti-IgM plus IL-4. The augmentation induced by anti-CD40 was inhibited by addition of anti-IL4 to anti-CD40-treated atopic dermatitis cells. In normal subjects the effects of anti-CD40 alone on IgE production could be observed after pretreatment of normal PBMCs with IL-4 for 3 days. The effects of anti-CD40 in atopic dermatitis may be explained in part by differences in CD40 expression. In freshly isolated PBMCs from patients with atopic dermatitis, the mean fluorescence intensity of CD40 expression on B cells was increased when compared with PBMCs from nonatopic donors, ans stimulation of normal or atopic dermatitis PBMCs with IL-4 increased the intensity of CD40 staining of cells.

Adolescent↗

PubMed1994

Increased acetylcholine release in tracheas from allergen-exposed IgE-immune mice.

Increased release of acetylcholine (ACh) from airway parasympathetic nerve endings is one mechanism that may contribute to increases in airway responsiveness in immunoglobulin E (IgE)-immune allergen-exposed animals. We measured ACh released from murine tracheas following electrical field stimulation in vitro. BALB/c mice were immunized by exposure to an aerosol of 1% ovalbumin in sterile phosphate-buffered saline for 20 min/day for 10 days. At this time, levels of ovalbumin-specific IgE were proportionately higher than ovalbumin-specific IgG. As a control, nonimmune mice were similarly exposed to phosphate-buffered saline alone. Forty-eight hours after the last aerosol, tracheas were removed for assessment of either the contractile responses to electrical field stimulation and a cholinergic agonist (methacholine or ACh) or release of ACh produced by electrical field stimulation. ACh in the bath was measured using high-performance liquid chromatography with electrochemical detection. The stimulation frequencies causing one-half the maximal contractile response to electrical field stimulation were 4.1 +/- 0.2 and 2.8 +/- 0.2 Hz (P = 0.0001) for nonimmune and immune mice, respectively, whereas the molar concentrations of methacholine causing one-half of the maximal contractile response did not significantly differ. In addition, the dose-response curves of immune and nonimmune tracheas to ACh were superimposable. A significant increase in ACh release was demonstrated at both 10 and 20 Hz in tracheas from immune mice. ACh release (pmol.g tissue-1.min-1) from nonimmune and immune murine tracheas, respectively, were 140 +/- 8 and 205 +/- 22 (P = 0.013) at 10 Hz and 147 +/- 13 and 227 +/- 14 (P = 0.008) at 20 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1994

Increased airways responsiveness in mice depends on local challenge with antigen.

In Balb/C mice, painting the skin with ovalbumin (OVA) over a period of 14 days resulted in sensitization of the animals. This was documented by the appearance of OVA-specific IgE and IgG1 antibodies and increased total serum IgE levels. In addition, in regional (inguinal) lymph nodes of sensitized animals, OVA-specific T cell proliferative responses and increased IgE and IgG production could be detected in vitro. Sensitized animals also developed immediate cutaneous responses to intradermal injection of OVA. In contrast to previous results following OVA sensitization via the airways, increased airways responsiveness to electrical field stimulation (AREFS) of tracheal smooth muscle preparations was not observed in skin-sensitized mice. Only 24 h after a single local challenge of the airways with aerosolized OVA on Day 14 could a significant increase in AREFS be observed in skin-sensitized but not nonsensitized control mice. These data indicate that sensitization of Balb/C mice to OVA via the skin provides an effective means for inducing a systemic IgE and IgG1 antibody response and immediate cutaneous hypersensitivity. Despite these IgE and IgG1-mediated responses, however, the development of altered function as reflected in an increase in AREFS was dependent on challenge with the allergen via the airways.

Administration, Cutaneous↗

PubMed1994

[New experimental therapies for type I allergy].

CD4+ T cells play a central role in the development of the immediate-type allergic response. It was shown that T cells from allergic patients exhibit an imbalance on the level of cytokine production which is characterized by increased IL-4- and decreased IFN-gamma production. Different strategies were developed to therapeutically interfere on various levels of the immunological dysregulation. In this article, the use of the immunomodulatory and immunosuppressive drugs methotrexate, cyclosporine, and intravenous immunoglobulin (IVIG) will be discussed. Furthermore, new experimental therapeutic approaches will be presented which are aimed to selectively interfere on the level of cytokine production and regulation. A different approach targets the functional activity of allergen-specific T cells whose functions could be modulated in an animal model system by subcutaneous treatment with peptides.

Animals↗

PubMed1993

Comparison of the allergenicity of ovalbumin and ovalbumin peptide 323-339. Differential expansion of V beta-expressing T cell populations.

We analyzed the effects of sensitization of BALB/c mice to the OVA peptide amino acids 323-339, on the development of an IgE response, immediate cutaneous hypersensitivity and airways responsiveness (AR). Daily aerosolization of OVA 323-339 for 20 min over a period of 10 days was as effective in the stimulation of a serum anti-OVA IgE antibody response as sensitization to native OVA by the same route. After sensitization to native OVA, the majority of the IgE anti-OVA response was directed against peptide 323-339. The antibody responses were paralleled by skin test responses in sensitized mice: 73% of OVA-sensitized mice developed immediate type reactions when tested with native OVA and 82% of the mice had positive immediate skin test responses to intradermal injection of peptide 323-339. After sensitization to the peptide, 69% of the mice had positive responses to native OVA and 77% responded to peptide 323-339. Aerosolization of OVA as well as OVA 323-339 led to a comparable increase in airway responsiveness as measured by electrical field stimulation of tracheal smooth muscle preparations. To characterize T cell subpopulations that were stimulated after allergen sensitization, the distribution of specific V beta-expressing T cells was analyzed in local draining lymph nodes of the airways and the lungs. These lymph nodes were found to be enlarged after both OVA and OVA peptide sensitization. Sensitization to native OVA resulted in an increased percentage of V beta 8.1 and V beta 8.2 T cells whereas selective stimulation of V beta 8.1 T cells was found after peptide sensitization. These data indicate that OVA peptide 323-339 represents a T and B cell epitope of OVA, which is important in the generation and development of immediate hypersensitivity responses in BALB/c mice.

Airway Resistance↗

PubMed1993

Specific V beta T cell subsets mediate the immediate hypersensitivity response to ragweed allergen.

T and B cell responses after sensitization to ragweed (RW) were examined in a mouse model in which BALB/c mice were exposed to the allergen by ultrasonic nebulization. Sensitization resulted in the stimulation of an IgE anti-RW response and was paralleled by a rise in IgG1 anti-RW titers. Skin testing for immediate cutaneous hypersensitivity revealed the presence of allergic type I reactions to RW. Sensitization to RW in this way was also associated with the development of increased airways responsiveness as determined by electrical field stimulation of preparations of tracheal smooth muscle. Histologic examination of the airways and the lung indicated the presence of a mononuclear cell infiltrate in the mucosa and submucosa of the airways that was accompanied by an enlargement of local draining lymph nodes of the airways and the lung. T cell populations were analyzed for the frequency of V beta-expressing T cells. Such analysis indicated that RW sensitization stimulated the expression of V beta 8.1+, V beta 8.2+, and V beta 13+ T cells in the local lymphoid tissue and of V beta 8.1+, V beta 8.2+, V beta 8.3+, V beta 9+ and V beta 14+ T cells in the spleen. Co-culture of these T cell populations with RW-primed B cells indicated that in the presence of RW, V beta 8.2 T cells stimulated IgE and IgG1 production, whereas the other T cell populations showed a different stimulation profile for Ig isotypes and IgG subclasses. The transfer of V beta 8.2 T cells from sensitized but not from nonsensitized control mice stimulated an allergen-specific IgE and IgG1 response and increased airways responsiveness in naive recipients. These data provide additional support for the pivotal role of specific V beta-expressing T cell subpopulations in the stimulation of IgE/IgG1 production and increased airways responsiveness.

Aerosols↗