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D M Kemeny

Publications and source records attributed to D M Kemeny.

At least 19 recordsLinked to original sources
PubMed1997

Antigen-specific CD8+ T cells inhibit IgE responses and interleukin-4 production by CD4+ T cells.

There is a growing body of evidence which suggests that CD8+ T cells play an important part in regulating the IgE response to non-replicating antigens. In this study we have systematically investigated their role in the regulation of IgE and of CD4+ T cell responses to ovalbumin (OVA) by CD8+ T cell depletion in vivo. Following intraperitoneal immunization with alum-precipitated OVA, OVA-specific T cell responses were detected in the spleen and depletion of CD8+ T cells in vitro significantly enhanced the proliferative response to OVA. Depletion of CD8+ T cells in vivo 7 days after immunization failed to enhance IgE production, while depletion of CD8+ T cells on days 12-18 greatly enhanced the IgE response, which rose to 26 micrograms/ml following a second injection of anti-CD8 on day 35 and remained in excess of 1 microgram/ml over 300 days afterwards. Reconstitution on day 21 of rats CD8-depleted on day 12 with purified CD8+ T cells from animals immunized on day 12 completely inhibited the IgE response. This effect was antigen specific; CD8+ T cells from OVA-primed animals had little effect on the IgE response of bovine serum albumin immunized rats. In vivo, CD8+ T cell depletion decreased interferon (IFN)-gamma production but enhanced interleukin (IL)-4 production by OVA-stimulated splenic CD4+ T cells. Furthermore, CD8+ T cell depletion and addition of anti-IFN-gamma antibody enhanced IgE production in vitro in an IL-4-supplemented mixed lymphocyte reaction. These data clearly show that antigen-specific CD8+ T cells inhibit IgE in the immune response to non-replicating antigens. The data indicate two possible mechanisms: first, CD8+ T cells have direct inhibitory effects on switching to IgE in B cells and second, they inhibit OVA-specific IL-4 production but enhance IFN-gamma production by CD4+ T cells.

Animals↗
PubMed1997

Corticosteroids restore the balance between locally produced Th1 and Th2 cytokines and immunoglobulin isotypes to normal in sarcoid lung.

In this study, we have investigated the balance between Th1- and Th2-like activity in the lungs in sarcoidosis and have determined the effect of corticosteroid treatment on this. Twenty-one patients with acute untreated sarcoidosis were investigated by bronchoalveolar lavage (BAL) and compared with 11 normal volunteers. Sixteen of the sarcoid patients required corticosteroid therapy and seven of these were reinvestigated after 2-3 months' treatment. In order to assess Th1- and Th2-like activity in the lungs, IgG subclasses and IgE were measured in BAL fluid and serum, and IL-2, IL-4 and interferon-gamma (IFN-gamma) in BAL. In patients with untreated sarcoidosis, albumin-corrected BAL/serum ratios for IgG4 and IgE were significantly reduced (IgG4, 1.04 +/- 0.18 (mean +/- s.e.m.); IgE 9.58 +/- 3.11) compared with those in normal controls (IgG4 5.3 +/- 0.72, P < 0.001; IgE 67.7 +/- 28.9, P < 0.01). Estimates of actual levels of immunoglobulins produced in the lungs were also made and showed extremely high levels of total IgG in sarcoid patients (39.56 +/- 8.2 mg/l) compared with controls (1.17 +/- 0.5 mg/l, P < 0.001). Although there was no difference between the groups in amount of IgG4 locally produced, the proportion of total IgG which was IgG4 was greatly reduced in those with sarcoidosis (1.6 +/- 0.4% compared with 38.5 +/- 3.2%; P < 0.001). Lavage levels of IL-4 were also reduced in sarcoid patients (IL-4 2.103 +/- 0.21 pg/ml) compared with those in normals (IL-4 6.8 +/- 1.05; P < 0.001). Levels of IL-2 were lower (7.63 +/- 0.51 pg/ml compared with 9.4 +/- 0.95 pg/ml), but this difference was not significant. IFN-gamma, however, could not be detected above 0.4 pg/ml in any of the normal lavage fluid, but was detectable in 12/21 patients with sarcoidosis (chi2 = 7.74; P < 0.001). These changes reverted towards normal on treatment with oral corticosteroids. The mean albumin-corrected BAL/serum ratio for IgG4 before treatment was 0.88 +/- 0.33 compared with 5.5 +/- 2.1 (P < 0.05) on treatment, and for IgE before treatment 9.52 +/- 2.15 compared with 50.8 +/- 17.9 (P < 0.05) on treatment. Total IgG produced in the lung fell from 26.16 +/- 7.9 to 6.12 +/- 2.4 mg/l (P < 0.001) on treatment, and the proportion of IgG4 locally produced rose from 2.3 + 0.8% to 23.9 +/- 6.1% (P < 0.01). The mean level of IL-4 in lavage before treatment was 2.53 +/- 0.34 pg/ml compared with 4.7 +/- 0.34 (P < 0.001) on treatment. Levels of IL-2 also rose significantly on treatment from 8.74 +/- 0.95 pg/ml before to 14.44 +/- 1.38 pg/ml (P < 0.001) on treatment. Levels of IFN-gamma fell from 1.65 +/- 0.43 pg/ml before treatment to undetectable levels in all patients (P < 0.001) on treatment. These results demonstrate an imbalance between Th1- and Th2-like activity in the lungs in sarcoidosis, with suppression of Th2 and increase in Th1. Corticosteroid therapy restores the normal balance between Th1 and Th2 cytokines and immunoglobulins in the lungs, suggesting an effect on local immune regulation.

Adolescent↗
PubMed1997

Immune memory in CD4+ CD45RA+ T cells.

This study addresses the question of whether human peripheral CD4+ CD45RA+ T cells possess antigen-specific immune memory. CD4+ CD45RA+ T cells were isolated by a combination of positive and negative selection. Putative CD4+ CD45RA+ cells expressed CD45RA (98.9%) and contained < 0.1% CD4+ CD45RO+ and < 0.5% CD4+ CD45RA+ CD45RO+ cells. Putative CD45RO+ cells expressed CD45RO (90%) and contained 9% CD45RA+ CD45RO+ and < 0.1% CD4+ CD45RA+ cells. The responder frequency of Dermatophagoides pteronyssinus-stimulated CD4+ CD45RA+ and CD4+ CD45RO+ T cells was determined in two atopic donors and found to be 1:11,314 and 1:8031 for CD4+ CD45RA+ and 1:1463 and 1:1408 for CD4+ CD45RO+ T cells. The responder frequencies of CD4+ CD45RA+ and CD4+ CD45RO+ T cells from two non-atopic, but exposed, donors were 1:78031 and 1:176,903 for CD4+ CD45RA+ and 1:9136 and 1:13,136 for CD4+ CD45RO+ T cells. T cells specific for D. pteronyssinus were cloned at limiting dilution following 10 days of bulk culture with D. pteronyssinus antigen. Sixty-eight clones were obtained from CD4+ CD45RO+ and 24 from CD4+ CD45RA+ T cells. All clones were CD3+ CD4+ CD45RO+ and proliferated in response to D. pteronyssinus antigens. Of 40 clones tested, none responded to Tubercule bacillus purified protein derivative (PPD). No difference was seen in the pattern of interleukin-4 (IL-4) or interferon-gamma (IFN-gamma) producing clones derived from CD4+ CD45RA+ and CD4+ CD45RO+ precursors, although freshly isolated and polyclonally activated CD4+ CD45RA+ T cells produced 20-30-fold lower levels of IL-4 and IFN-gamma than their CD4+ CD45RO+ counterparts. Sixty per cent of the clones used the same pool of V beta genes. These data support the hypothesis that immune memory resides in CD4+ CD45RA+ as well as CD4+ CD45RO+ T cells during the chronic immune response to inhaled antigen.

Allergens↗
PubMed1997

Regulation of cytokine production by human Th0 cells following stimulation with peptide analogues: differential expression of TGF-beta in activation and anergy.

The different biological activities of T-cell-derived cytokines and their level of production influences the qualitative nature of immune responses and, in certain forms of T-cell tolerance, the lack of antigen responsiveness is associated with the production of transforming growth factor-beta (TGF-beta) and interleukin-4 (IL-4). In this study we have investigated the effects of T-cell receptor (TCR) ligation with peptide analogues and the native peptide, in the presence and absence of costimulation, on cytokine production by human T-helper type 0 (Th0) cells reactive with influenza virus haemagglutinin (HA) peptide (HA306-318) and restricted by HLA-DRB1*0101. We observed that resting Th0 cells constitutively produced TGF-beta, but when stimulated with peptide and antigen-presenting cells (APC) under conditions that induce clonal expansion, TGF-beta secretion was abrogated. Furthermore, exposure of the T cells to the wild-type HA peptide under conditions that induce T-cell anergy resulted in the secretion of TGF-beta, and subsequent antigenic rechallenge was unable to override this signal and down-regulate TGF-beta production. Stimulation with altered TCR ligands that failed to induce proliferation also resulted in marked production of TGF-beta, although in many instances the levels were less than those observed in the total absence of antigen, suggesting that partial signalling has occurred. Although in general, there was a direct positive correlation between proliferation and the production of IL-2, IL-4 and interferon-gamma (IFN-gamma) following stimulation with certain analogues, the production of selected cytokines was dissociated.

Amino Acid Sequence↗
PubMed1997

GM-CSF increases the ability of cultured macrophages to support autologous CD4+ T-cell proliferation in response to Dermatophagoides pteronyssinus and PPD antigen.

Previous studies have demonstrated an infiltration of monocytes and increased levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the asthmatic lung. To study the possible effects of this cytokine upon the differentiation and function of these newly recruited monocytes, we have developed a model in which monocytes isolated from human peripheral blood were differentiated into macrophages in serum in the presence or absence of GM-CSF. After 7 days, the macrophages increased in size and granularity, had increased phagocytic activity, and expressed various adhesion molecules, CD14 and major histocompatibility complex (MHC) class II. The effects of GM-CSF on antigen presentation by cultured macrophages on the antigen-specific proliferative response of CD4+ T cells to Dermatophagoides pteronyssinus or purified protein derivative of tuberculin and the mitogen phytohaemagglutinin was determined. CD4+ T-cell proliferation was reduced when either antigen was presented by macrophages cultured in serum alone, compared with the values obtained with freshly isolated monocytes. However, CD4+ cell proliferation was comparable to that observed with monocytes when antigen was presented by macrophages which had been pre-cultured with 50 U/ml GM-CSF. CD4+ T-cell proliferation to phytohaemagglutinin was similar when all three populations were used as accessory cells. High numbers of macrophages partially suppressed CD4+ T-cell proliferation in response to antigen presented by monocytes, but there was no significant difference between macrophages cultured in the presence or absence of GM-CSF. This data suggests that GM-CSF directs monocyte differentiation into macrophages with an antigen-presenting, rather than a suppressive, phenotype. Elevated levels of GM-CSF in the asthmatic lung may therefore maintain recently recruited monocytes in an inflammatory and T-cell activating state.

Antigen Presentation↗
PubMed1997

Adoptive transfer of allergen-specific CD4+ T cells induces airway inflammation and hyperresponsiveness in brown-Norway rats.

Following allergen exposure, sensitized Brown-Norway rats develop airway hyperresponsiveness (AHR) and eosinophilic inflammation together with an increase in activated T cells (CD25+) in the airways. We tested the hypothesis that CD4+ T cells are involved directly in the acquisition of AHR. Spleen T cells from animals that were injected intraperitoneally on three consecutive days with ovalbumin/Al(OH)3, showed a dose-dependent proliferative response in vitro to ovalbumin, but not to bovine serum albumin, as measured by [3H]thymidine uptake. For total T-cell transfer, spleen cells obtained from donor rats 4 days after sensitization were depleted of adherent cells by a nylon wool column separation. CD4+ and CD8+ T cells were purified by immunomagnetic beads cell separation. Recipient naive rats were injected intravenously with 50 x 10(6) total T cells, 20 x 10(6) and 5 x 10(6) CD4+ cells, and 5 x 10(6) CD8+ cells, and were exposed to ovalbumin aerosol 24 hr afterwards. After a further 24 hr, airway responsiveness to acetylcholine (ACh) was measured and provocative concentration (PC) values PC100, PC200 and PC300) (the ACh concentration needed to achieve 100, 200 and 300% increase in lung resistance above baseline) were calculated. Airway responsiveness was significantly increased in recipients of sensitized total T cells compared with recipients of cells from saline-injected donor rats (P < 0.05). There were significantly increased eosinophil major basic protein (MBP)+ cell counts/mm2 in airway submucosal tissue in the hyperreactive rats and a significant correlation was found between the number of MBP+ cells and PC100 (r = 0.75; P < 0.03) in recipients of sensitized total T cells. Purified CD4+ T cells from sensitized donors induced AHR in naive recipients (P < 0.05), while sensitized CD8+ and naive CD4+ cells failed to do so. Our data indicate that T cells may induce AHR through an eosinophilic airway inflammation and that CD4+ T cells may have a direct effect in this process in Brown-Norway rats.

Adoptive Transfer↗
PubMed1996

Contribution of CD4+ and CD8+ T lymphocyte subsets to the cytokine secretion patterns induced in mice during sensitization to contact and respiratory chemical allergens.

Chemical allergens of different types, those that cause in humans allergic contact dermatitis or occupational asthma induce in mice divergent immune responses characteristic, respectively, of T-helper 1 (Th1)- and Th2-type cell activation. Such responses are associated with the development of different cytokine secretion patterns by draining lymph node cells (LNC), such that contact allergens stimulate vigorous interferon-gamma (IFN-gamma) production, but little secretion of the Th2 cytokines interleukin-4 and interleukin-10 (IL-4 and IL-10), whereas the converse pattern is provoked by respiratory allergens. Using selective depletion with antibody and complement we have here examined the relative contribution of CD4+ and CD8+ T lymphocytes to the cytokine secretion patterns of draining LNC isolated from mice sensitized to chemical allergens. Mice received repeated topical applications of respiratory allergens, trimellitic anhydride (TMA) or diphenylmethane diisocyanate (MDI), or of contact allergens 2,4-dinitrochlorobenzene (DNCB) or formaldehyde. Thirteen days following the initiation of exposure the production by draining LNC of IL-10, IFN-gamma and mitogen (concanavalin A)-inducible IL-4 was measured by enzyme-linked immunosorbent assay (ELISA) after various periods of culture. It was found that the high levels of IL-4 and IL-10 secretion stimulated by TMA or MDI, and the lower levels of these cytokines induced by DNCB or formaldehyde, were in all cases dependent upon the presence of CD4- cells. In contrast, the comparatively high concentrations of IFN-gamma observed following exposure to contact allergens were found to be derived from CD4+ cells, and in the case of DNCB from CD8+ cells also. The low levels of IFN-gamma induced by treatment with TMA or MDI were associated largely or wholly with CD8+ cells. These data indicate that the type 2 cytokine responses induced to different extents by both contact and respiratory chemical allergens are almost exclusively a function of CD4+ cells, but that IFN-gamma is produced by either CD4+ cells in the case of contact allergens or largely by CD8+ cells in the case of chemical respiratory allergens.

Allergens↗
PubMed1996

Expression of Th-2 cytokines interleukin-4 and -5 and of Th-1 cytokine interferon-gamma in ovalbumin-exposed sensitized Brown-Norway rats.

We determined the expression of Th-2 type cytokines, interleukin-4 (IL-4) and IL-5, and of the Th-1 type cytokine, interferon-gamma (IFN-gamma), in the Brown-Norway rat. Rats were intraperitoneally sensitized with ovalbumin and 21 days later were either exposed to ovalbumin or saline aerosol. The value -log PC300 (PC300 = concentration of acetylcholine needed to increase baseline lung resistance by 300%) was 2.49 +/- 0.15 in sensitized, exposed rats, was higher than in sensitized, saline-exposed or naive rats (1.54 +/- 0.27 and 1.63 +/- 0.06 respectively, P < 0.05). There was a significant increase in eosinophils in bronchoalveolar lavage fluid and in airway submucosal airway tissues in the sensitized exposed group. Reverse-transcriptase polymerase chain reaction was performed on total lung RNA using primers for IL-4, IL-5, IFN-gamma and beta-actin. IL-4 and IL-5 mRNA levels in control and sensitized saline-exposed rats were not detectable, but increased levels were found in sensitized and ovalbumin-exposed rats with levels of 0.25 +/- 0.01 and 0.98 +/- 0.02% of beta-actin mRNA as assessed by densitometric measurements. Expression of IFN-gamma mRNA was significantly reduced in sensitized and ovalbumin-exposed rats. As in asthmatic airways, there is an increased expression of Th-2 cytokines, IL-4 and IL-5, together with a reduction in the Th-1 cytokine, IFN-gamma, thus supporting a role for Th-2 cytokines in allergic eosinophilic inflammation.

Animals↗
PubMed1996

The contrasting effects of CD8+ T cells on primary, established and Nippostrongylus brasiliensis-induced IgE responses.

Recent data have indicated that CD8+ T cells suppress rodent IgE responses. In this study we investigated the effect of CD8+ T cells on primary and established IgE responses in euthymic and athymic nude rats. Euthymic PVG rats were depleted of CD8+ T cells by intraperitoneal injection of a CD8-specific monoclonal antibody (OX8), which resulted in an apparent loss of 92% of splenic and 98% of peripheral blood CD8+ T cells. The CD8+ T-cell depleted animals failed to mount a significant IgE response compared with control animals given an irrelevant monoclonal antibody (OX21). Furthermore, PVG nude rats reconstituted with purified CD4+ thoracic duct lymphocytes (TDL) alone failed to mount a significant IgE response, while animals given unfractionated TDL (containing CD4+ and CD8+ T cells) did. Depletion of CD8+ T cells 7 days prior to immunization and subsequent reconstitution at the time of immunization restored the IgE response. In contrast, removal of CD8+ T cells 1 month after induction of IgE by immunization with ovalbumin (OVA) and ricin prolonged the IgE response. In all cases IgG antibody responses were unaffected by the presence or absence of CD8+ T cells. This study shows that some CD8+ T cells are required for IgE, but not IgG, production to soluble antigen in a primary immune response. However, later in the immune response CD8+ T cells were shown to inhibit IgE production. These effects were apparently restricted to the immune response to soluble antigen, as Hooded Lister rats infected with 9000 larvae of the nematode Nippostrongylus brasiliensis produced high sustained levels of circulating IgE, in excess of 10 micrograms/ml, regardless of whether CD8+ T cells were depleted before or 1 month after infection.

Animals↗
PubMed1995

IFN-gamma and IL-4 regulate the growth and differentiation of CD8+ T cells into subpopulations with distinct cytokine profiles.

In this study, we have investigated the effects of IL-4 and IFN-gamma on the growth and differentiation of CD8+ T cells in vitro. Rat splenic CD8+ T cells expressed higher levels of IL-4, IL-5, IL-10, and IFN-gamma mRNA, as measured by reverse-transcription PCR, than CD4+ T cells from the same source, whereas CD4+ T cells expressed more IL-2 and IL-6 mRNA. CD8+ T cells were cultured for 6 days with PMA, ionomycin, and IL-2, and their ability to proliferate, to express mRNA for IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma, and to secrete IFN-gamma and IL-2 was determined. IL-4 could act as a growth factor for CD8+ T cells during primary stimulation, but inhibited proliferation of the restimulated 6-day-cultured CD8+ T cells. The highest levels of mRNA for IL-2 and IL-6 were detected in control cultures in which little mRNA for IL-4, IL-5, or IL-10 was detected. Addition of IL-4 to the primary cultures reduced the capacity of the restimulated cells to express mRNA for IL-2, and for IL-6, but enhanced expression of mRNA for IL-4 and IL-5. Addition of IFN-gamma to the cultures, alone or in conjunction with IL-4, or addition of IFN-gamma-specific neutralizing Ab, had little effect. However, in conjunction with IL-4, anti-IFN-gamma enhanced expression of mRNA for IFN-gamma, and for IL-10. These results indicate that IL-4 and IFN-gamma regulate the differentiation of CD8+ T cells and the growth of cytotoxic and other types of CD8+ T cells, and suggest pathways through which CD8+ T cells may interact with other immune cells.

Animals↗
PubMed1995

The role of CD8+ T cells in immunoglobulin E regulation.

The link between immunoglobulin E (IgE) antibodies and environmental allergens, allergic sensitization and atopic diseases such as asthma, rhinitis and eczema is well established, yet treatment of these diseases is largely symptomatic and fails to correct the underlying immune disorder. B-cell production of IgE depends on interleukin 4 (IL-4) and is inhibited by interferon (IFN-gamma). These cytokines are produced by T-helper 2 (Th2) and T-helper 1 (Th1) CD4+ T cells respectively. In atopic dermatitis skin and asthmatic lung, Th2 cells predominate but antigen-specific CD4+ T-cell clones derived from peripheral blood are a mixture of Th1, Th2, and Th0. Circulating allergen-specific CD4+ T cells differentiate into Th1- and Th2-like clones in the presence of IL-12 and IL-4 respectively. In rats, CD8+ T cells are potent regulators of IgE responses in vivo, although the mechanism for this is still unclear. CD8+ T-cell depletion in immunized animals prolonged the IgE response but prior depletion did not. Indeed, prior depletion of CD8+ T cells actually inhibited IgE production, suggesting that there may be more than one type of IgE regulatory CD8+ T cell. This was supported by the observation that CD8+ T cells inhibited the differentiation of both Th1 and Th2 CD4+ T cells in vitro as well as IL-4- but not IL-2-induced Th2 CD4+ T-cell growth. The existence of distinct CD8+ T-cell subsets is supported by the observation that IL-4 and IFN-gamma regulate the growth and differentiation of CD8+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Interleukin-4 enhances interferon-gamma synthesis but inhibits development of interferon-gamma-producing cells.

Interleukin-4 (IL-4) is antagonistic for many of the activities of interferon-gamma (IFN-gamma) and, as well as suppressing the development of T-helper type-1 (Th1) cells, has been reported to block directly the synthesis of IFN-gamma in human lymphocytes. However, IL-4 transgenic mice produce increased amounts of IFN-gamma as well as IL-4. We have compared the ability of rat IL-4 to regulate IFN-gamma secretion in short-term cultures of spleen cells with its effect on the differentiation of T lymphocytes into IFN-gamma-producing, or Th1-type, cells. Normal rat spleen cells were stimulated using a variety of mitogens and ovalbumin antigen, with or without IL-4, for 12-24 hr and the levels of IFN-gamma in the supernatants measured by enzyme-linked immunosorbent assay (ELISA). The results show that when normal rat splenocytes were stimulated with phytohaemagglutinin (PHA) or concavalin A (Con A), IL-4 enhanced secretion of IFN-gamma after 12-24 hr. This enhancement was also apparent when splenocytes from animals immunized 10 days previously with alum-precipitated ovalbumin were stimulated with ovalbumin in vitro, and appeared to be mediated primarily via CD+ T cells. In contrast, when spleen cells were maximally stimulated with phorbol myristate acetate (PMA) and ionomycin, addition of IL-4 had no effect on the amount of IFN-gamma secreted. When splenocytes were stimulated with Con A for 4 days in the presence of IL-4, and restimulated with PMA and ionomycin, IFN-gamma secretion was greatly suppressed. Our results indicate that IL-4 exerts differential effects on IFN-gamma secretion and on the development of IFN-gamma-producing lymphocytes.

Animals↗
PubMed1995

IgE production, antigen-induced airway inflammation and airway hyperreactivity in the brown Norway rat: the effects of ricin.

Ricin has been shown to enhance IgE production in the rat, probably through inhibition of suppressor T lymphocytes. We have studied further the effects of ricin on IgE titre and have determined its effects on antigen-induced airway inflammation and hyperreactivity in the Brown Norway rat. Immunization with ovalbumin (1-100 micrograms, intraperitoneally) produced dose-related increases in serum antigen-specific IgE titre. Ricin augmented the total IgE titre and caused about a 10-fold increase in the peak antigen-specific IgE titre. In sensitized animals, antigen challenge (three times with aerosolized ovalbumin every second day) caused a significant influx of eosinophils and neutrophils and significant airway hyperreactivity 24 hr after the third challenge. In sensitized animals that had also received ricin, the eosinophil and neutrophil influx was further significantly potentiated and a significant influx of lymphocytes also occurred. Thus, there was a relationship between the degree of sensitization and the magnitude of the inflammatory response. However, the enhanced airway inflammation in ricin-treated animals was not accompanied by a further enhancement of airway hyperreactivity. The present study demonstrates that ricin enhances IgE production and augments an antigen-induced inflammatory pathology but does not potentiate antigen-induced airway hyperreactivity.

Animals↗
PubMed1994

Immune regulation: a new role for the CD8+ T cell.

During an immune response, peripheral T cells develop into functionally distinct subpopulations that effect cell-mediated immunity and regulate humoral immune responses through the secretion of specific cytokines. Recent data suggest that CD8+ T cells, which have long been regarded simply as cytotoxic cells, play a more active role in the regulation of the immune response. In this article, Mike Kemeny and colleagues suggest that there are functionally distinct subsets of CD8+ T cells that produce different combinations of cytokines and appear to play an important part in determining the pattern of cytokines produced by CD4+ T cells and the isotype of immunoglobulins expressed by B cells.

Animals↗
PubMed1994

Specificity of ELISA for IgG subclass antibodies against inhalant antigens in early childhood.

ELISA is increasingly used to measure antibodies in new circumstances. Recently, it has been applied to the measurement of IgG subclass antibodies against common antigens in early childhood. These studies have raised concerns about the specificity of some of these assays. This paper details the results of experiments which have assessed the specificity of IgG1 binding to allergens of dust mite (Dermatophagoides pteronyssinus) and ryegrass (Lolium perenne) pollen by inhibition ELISA in the sera of 2-year-old children of atopic parents. Six sera which showed binding of IgG1 to D. pteronyssinus and six to L. perenne were used. All had IgG1 antibody against ovalbumin. In the children's sera, binding to D. pteronyssinus was substantially inhibited by preincubation with the homologous antigen, but not with ovalbumin, thereby confirming the specificity of the assay. However, suppression of IgG1 binding to L. perenne with the homologous antigen was comparatively small, and ovalbumin could cause an equivalent inhibition, indicating poor specificity. Furthermore, the level of IgG1 binding to L. perenne was closely correlated to the level of IgG1 binding to ovalbumin (r = 0.98; P < 0.001). When the assay was reversed, IgG1 binding to ovalbumin was only slightly inhibited by L. perenne, indicating that most antibody binding to ovalbumin was specific. Thus, binding IgG1 in both adult and child sera to D. pteronyssinus appeared to be specific, while child, but not adult, IgG1 binding to L. perenne showed poor specificity. This disparity may be due to differences in the affinities of the respective antibodies, and it illustrates the importance of determining assay specificity when making measurements in early childhood.

Adult↗
PubMed1993

An analysis with sequence-specific oligonucleotide probes of the association between aspirin-induced asthma and antigens of the HLA system.

BACKGROUND: Previous work has suggested that in addition to environmental influences, there is a genetic predisposition for the development of both asthma and atopy. A subset of asthmatic subjects who are intolerant to aspirin has been identified. A previous study has suggested that there is an association between aspirin sensitivity and HLA-DQw2. METHODS: To further assess this association, we studied two populations of aspirin-sensitive subjects and aspirin-tolerant subjects with asthma. Genomic DNA was amplified by polymerase chain reaction and hybridized with radiolabeled oligonucleotide probes specific to the second exon of the DRB1, DQA1, DQB1, and DPB1 chains. RESULTS: Using polymerase chain reaction amplification of genomic DNA and sequence-specific oligonucleotide probes, we have been unable to confirm a significant association between aspirin sensitivity and HLA-DQw2. CONCLUSION: We have shown, however, that there is a significant decrease in the incidence of DPB1*0401 in both aspirin-tolerant and aspirin-intolerant subjects with asthma in both populations studied.

Adolescent↗