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D T Umetsu

Publications and source records attributed to D T Umetsu.

At least 73 records · Page 4Linked to original sources
PubMed1993

Allergen immunotherapy decreases interleukin 4 production in CD4+ T cells from allergic individuals.

Allergen specific CD4+ T cell clones generated from allergic individuals have been shown to produce increased levels of the cytokine interleukin 4 (IL-4), compared to allergen specific clones generated from nonallergic individuals. This difference between CD4+ T cells from allergic and nonallergic individuals with regard to cytokine production in response to allergen is thought to be responsible for the development of allergic disease with increased IgE synthesis in atopic individuals. We examined the production of IL-4 in subjects with allergic rhinitis and in allergic individuals treated with allergen immunotherapy, a treatment which involves the subcutaneous administration of increasing doses of allergen and which is highly effective and beneficial for individuals with severe allergic rhinitis. We demonstrated that the quantity of IL-4 produced by allergen specific memory CD4+ T cells from allergic individuals could be considerably reduced by in vivo treatment with allergen (allergen immunotherapy). Immunotherapy reduced IL-4 production by allergen specific CD4+ T cells to levels observed with T cells from nonallergic subjects, or to levels induced with nonallergic antigens such as tetanus toxoid. In most cases the levels of IL-4 produced were inversely related to the length of time on immunotherapy. These observations indicate that immunotherapy accomplishes its clinical effects by reducing IL-4 synthesis in allergen specific CD4+ T cells. In addition, these observations indicate that the cytokine profiles of memory CD4+ T cells can indeed be altered by in vivo therapies. Thus, the cytokine profiles of memory CD4+ T cells are mutable, and are not fixed as had been suggested by studies of murine CD4+ memory T cells. Finally, treatment of allergic diseases with allergen immunotherapy may be a model for other diseases which may require therapies that alter inappropriate cytokine profiles of memory CD4+ T cells.

Adult↗
PubMed1993

In vitro synthesis of IL-4 by human CD4+ T cells requires repeated antigenic stimulation.

Although Th2 helper cell clones produce IL-4 and IL-5, CD4+ T cells taken fresh from lymphoid organs of mice produce IL-2 and some IFN-gamma, but not IL-4 or IL-5. The exact parameters that enhance the synthesis of IL-4, IL-5, and particularly IL-10 from resting antigen-specific CD4+ T cells is not yet clear. We therefore examined the kinetics of, and the parameters that affect, the development of IL-4, IL-5, and IL-10 production in bulk populations of antigen-specific human CD4+ T cells. We demonstrated that in vitro stimulation of human peripheral blood lymphocytes with antigen (tetanus toxoid or a viral antigen, Varicella zoster) for several days resulted in the production of IL-2 and IFN-gamma, but little or no IL-4 or IL-5. This cytokine profile was observed even when CD4+ T cells from allergic donors were stimulated once in vitro with allergen (rye grass pollen, Lolium perenne I, or dust mite allergen, Dermatophagoides farinae). The observed cytokine profile reflected that of the vast majority of antigen-specific T cells, since we studied the response of bulk populations of CD4+ T cells rather than that of a "selected" number of antigen-specific T cell clones. Furthermore, we observed that human CD4+ T cells from either allergic or nonallergic individuals failed to produce significant quantities of IL-4, IL-5, or IL-10 even after several rounds of stimulation with soluble protein (nonallergen) antigens such as tetanus toxoid or Var. z. However, large quantities of these cytokines were produced when stimulation of the T cells occurred in the presence of rIL-4, but only after two stimulations in vitro with antigen over a period of greater than 7 days. In addition, substantial quantities of IL-4, IL-5, and IL-10 were produced by CD4+ T cells from allergic subjects in the absence of exogenous IL-4, but only after two stimulations in vitro with allergens such as rye grass pollen or dust mite allergen. These results indicate that the development of IL-4 and IL-5 synthesis occurs in peripheral blood CD4+ T cells in a stepwise fashion, first with the production of IL-2 and IFN-gamma, and later with the production of IL-4 and IL-5.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens↗
PubMed1993

Induction of immunoglobulin synthesis by CD4+ T cell clones.

The study of mechanisms by which CD4+ T cells induce Ig synthesis has been greatly enhanced by the availability of CD4+ T cell clones with restricted cytokine profiles. We have demonstrated with in vitro and in vivo studies that both Th1 (T helper cell 1) and Th2 clones can provide MHC restricted help and induce primary as well as secondary antibody responses under cognate antigen driven conditions. In addition, we have shown that both types of clones, utilizing distinct cytokines, can effect B cell memory and affinity maturation of the Ig response, although the precise mechanisms by which this occurs are not yet clear. Using Th1 and Th2 clones, we have also shown that the pathways for IgG1 synthesis are redundant, in that induction of IgG1 synthesis in secondary responses in which B cells have already switched from IgM to IgG1, can occur via several pathways, one involving IL-4 and IL-5, the other involving IL-2. In contrast, IgE and IgG2a synthesis require specific cytokines for synthesis in both primary and secondary B cells. Finally, the cytokines produced by Th1 and Th2 clones can 'neutralize' each other, when both types of clones are present during the induction of primary Ig responses. As an exception however, the induction of IgA synthesis is greatly augmented by the presence of both types of clones.

Animals↗
PubMed1992

IL-4 synthesis by in vivo primed keyhole limpet hemocyanin-specific CD4+ T cells. I. Influence of antigen concentration and antigen-presenting cell type.

The development of IL-4 synthesis is a critical step in the regulation of immune responses. Our studies focused on the production of IL-4 by CD4+ T cells taken from mice primed with the Ag keyhole limpet hemocyanin (KLH). In vitro stimulation of such CD4+ T cells with KLH resulted in little or no IL-4 production in the first 24 h of stimulation, indicating that little IL-4 synthesis persists in vivo after immunization. However, IL-4 was generated later at 24 to 96 h of in vitro stimulation, indicating that the potential to produce IL-4 was retained by the KLH-primed CD4+ T cells, but that in vitro maturation of the T cells was required before initiation of IL-4 production. The amount of IL-4 produced in vitro by KLH-primed T cells from BALB/c mice was influenced by several factors. First, stimulation of KLH-primed CD4+ T cells with higher in vitro concentrations of KLH resulted in more IL-4 synthesis, but this was accompanied by more IFN-gamma as well. Second, primed CD4+ T cells from lymph nodes (axillary and popliteal) produced significantly more IL-4 than primed splenic T cells. Third, when primed B cells were utilized to present low concentrations of KLH to the T cells, IL-4 but not IFN-gamma was produced. In contrast, use of splenic adherent cells resulted in IFN-gamma but not IL-4 synthesis. These restricted patterns of lymphokine synthesis, however, were observed only with low concentrations of KLH. Fourth, the amount of IL-4 produced and its regulation by the presence of IFN-gamma differed among mouse strains, in that BALB/c T cells produced much more IL-4 than H-2 identical DBA/2 T cells. Our results characterizing the APC and Ag dose requirements for IL-4 synthesis in KLH-primed T cells from different strains of mice are consistent with previous observations that distinct strains of mice differ in the type of immune response generated against different pathogens, and with the concept that low Ag concentrations preferentially result in high levels of IgE synthesis, which is absolutely dependent on IL-4 production.

Animals↗
PubMed1992

Generation of B cell memory and affinity maturation. Induction with Th1 and Th2 T cell clones.

We used an adoptive transfer system and CD4+ T cell clones with defined lymphokine profiles to examine the role of CD4+ T cells and the types of lymphokines involved in the development of B cell memory and affinity maturation. Keyhole limpet hemocyanin (KLH)-specific CD4+ Th2 clones (which produce IL-4 and IL-5 but not IL-2 or IFN-gamma) were capable of inducing B cell memory and affinity maturation, after transfer into nude mice or after transfer with unprimed B cells into irradiated recipients and immunization with TNP-KLH. In addition, KLH-specific Th1 clones, which produce IL-2 and IFN-gamma but not IL-4 or IL-5, were also effective in inducing B cell memory and high affinity anti-TNP-specific antibody. The induction of affinity maturation by Th1 clones occurred in the absence of IL-4, as anti-IL-4 mAb had no effect on the affinity of the response whereas anti-IFN-gamma mAb completely blocked the response. Th1 clones induced predominantly IgG2a and IgG3 antibody, although Th2 clones induced predominantly IgG1 and IgE antibody. We thus demonstrated that some Th1 as well as some Th2 clones can function in vivo to induce Ig synthesis. These results also suggest that a single type of T cell with a restricted lymphokine profile can induce both the terminal differentiation of B cells into antibody secreting cells as well as induce B cell memory and affinity maturation. Moreover, these results suggest that B cell memory and affinity maturation can occur either in the presence of Th2 clones secreting IL-4 but not IFN-gamma, or alternatively in the presence of Th1 clones secreting IFN-gamma but not IL-4.

Animals↗
PubMed1991

Differential regulation of antigen presentation in high- and low-IgE responder mice.

Strains of mice differ greatly in their capacity to produce interleukin (IL) 4 and high levels of serum IgE. The contribution of macrophages (M phi) in enhancing the production of IL4 by T cells in high-IgE responder mice was studied. M phi from BALB/c mice (high-IgE responder strain) developed an augmented capacity to present antigen to IL 4-producing T helper type 2 (Th2) clones, when the M phi were pretreated by exposure to the lymphokines IL 4 and IL 5. In contrast, identical treatment of M phi from H-2-identical DBA/2 mice (low-IgE responder strain) resulted in inhibition of the capacity to stimulate Th2 clones. The impairment of antigen presentation by DBA/2 M phi was closely paralleled by a decrease of cell surface class II major histocompatibility complex (MHC) expression and an abrogation of IL 1 production by these cells, while identical treatment of BALB/c M phi enhanced class II MHC expression and did not inhibit secretion of IL 1. Our studies demonstrate that IL 4 and IL 5 can exert different effects on M phi from high- and low-IgE responder strains of mice, resulting in down-regulation of the expansion of IL 4-producing cells in low-but not high-IgE responder mice.

Animals↗
PubMed1991

Follicular lymphoma: a model of lymphoid tumor progression in man.

Human follicular lymphoma can be viewed as a malignancy in evolution. Since this disease is composed of a clonal population of B lymphocytes all expressing a given immunoglobulin light chain and heavy chain, it seems possible that the initial transforming event, the t(14; 18) chromosomal translocation, occurs in a cell already committed to the expression of a particular VH and VL gene. A panel of antibodies has been assembled which define a set of idiotypes expressed repeatedly by B-cell lymphomas. Nonetheless, VH gene usage in follicular lymphoma tumors appears to reflect the normal B-cell repertoire. Growth of follicular lymphoma appears to be partially under normal regulatory control. The expanding malignant B-cell clone grows in follicles with particular apposition to follicular dendritic cells and heavy infiltration with CD4+ T cells. Interaction with T cells can induce the proliferation of follicular lymphoma cells. This tumor eventually evolves into a diffuse large-cell lymphoma which is highly aggressive and lethal. It is now clear that the malignant progression occurs from a single cell within the expanding follicular lymphoma clone. A panel of monoclonal antibodies to cell surface molecules has been generated that inhibit proliferation of diffuse lymphoma cell lines, and some of the target molecules have been partially characterized. Therapeutic application of anti-idiotype monoclonal antibodies has shown a high degree of tumor responsiveness, but ultimately escape of idiotype-negative variant cells occurs. These variants arise as a result of extensive somatic point mutation in the VH and VL genes of follicular lymphoma. Active immunization can result in an immune response by patients directed against the idiotype expressed on their own B-cell tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Communication↗
PubMed1990

Sinus disease in patients with severe cystic fibrosis: relation to pulmonary exacerbation.

Four adult cystic fibrosis patients were selected for aggressive surgical management of sinus disease on the basis of severe pulmonary involvement, high frequency of hospital admission, chronic headache, and wheezing unresponsive to conventional treatment. They underwent bilateral Caldwell-Luc procedure with perioperative anti-Pseudomonas antimicrobials. There were substantial improvements in headache and respiratory symptoms and a significant reduction in the frequency of hospital admission after the operation. These findings suggest that sinus disease is associated with pulmonary exacerbation in patients with cystic fibrosis, and strengthens a similar observation in patients with asthma.

Adolescent↗
PubMed1990

Induction of proliferation of human follicular (B type) lymphoma cells by cognate interaction with CD4+ T cell clones.

We examined stimuli which are required for the induction of in vitro proliferation of follicular lymphoma cells, a low grade non-Hodgkin's B cell lymphoma characterized by a specific chromosomal translocation, t(14;18)(q32;q21), and by in vivo growth of the lymphoma cells in germinal center-like follicles infiltrated with CD4+ T cells. The purified follicular lymphoma cells, which are morphologically uniform, small, and dense, did not respond to stimulation with soluble lymphokines in the absence of T cells. Vigorous in vitro proliferation of follicular lymphoma cells was induced, however, when the follicular lymphoma cells were cultured with a CD4+ T cell clone which recognized alloantigens expressed by the lymphoma cells. This response required B-T cell contact, and was inhibited by anti-class II but not by anti-class I MHC mAb, indicating that these neoplastic B cells behaved as normal B cells and responded to normal activation and differentiation signals from T cells. After the cognate B lymphoma-T cell interaction occurred in culture, addition of IL-2 or IL-4 enhanced the proliferation of the tumor cells. These results, with a monoclonal and homogeneous population of B cells, affirm the idea that cognate interaction between B cells and Th cells is required for the effective activation of resting B cells. Moreover, these results suggest that a critical host-tumor interaction occurs in vivo, and that the polyclonal CD4+ T cells that infiltrate follicular lymphomas play a role in sustaining rather than inhibiting tumor growth in vivo. If so, therapies directed not only against the neoplastic cell but also against specific T cells and their cognate interactions with tumor cells may have a rationale.

B-Lymphocytes↗
PubMed1990

Induction of antibody synthesis by CD4+ T cells: IL 5 is essential for induction of antigen-specific antibody responses by TH2 but not TH1 clones.

Murine B cells stimulated with lipopolysaccharide (LPS) and interleukin (IL) 4 produce IgG1 and IgE, but synthesize IgG2a when stimulated with LPS and interferon-gamma. The cytokines, however, that regulate immunoglobulin (Ig) synthesis induced in normal B cells under antigen-driven major histocompatibility complex (MHC)-restricted conditions in the absence of potent B cell mitogens have not been fully elucidated. We and others have shown that under cognate MHC-restricted conditions, CD4+ T cell clones of the TH1 subset, which produce IL 2 and interferon-gamma, and T cell clones of the TH2 subset, which produce IL 4 and IL 5, are both capable of inducing anti-trinitrophenyl IgG plaque-forming cells. In this report we have examined in further detail the cytokine requirements for the induction of Ig synthesis in B cells cultured directly with TH1 and TH2 T cell clones. Using (a) TH2 clones that varied in the amount of IL 5 secreted, (b) a neutralizing monoclonal antibody against IL 5 and (c) T cell clones pretreated with cyclosporin A to inhibit cytokine secretion, we found that IL 5 was essential for induction of IgG1 synthesis by TH2 but not TH1 T cells. Although we demonstrated that IL 2 could actually up-regulate the synthesis of IL 5 by TH2 clones, the induction of IgG synthesis by TH2 clones was entirely independent of IL 2. In contrast, induction of IgG1 synthesis by TH1 clones was absolutely dependent upon the presence of IL 2 and was not affected by the presence of IL 5. Thus, these studies demonstrate the idea that at least two independent pathways exist for the induction of IgG1 synthesis, and that one of these pathways is IL 4/IL 5 dependent and the other IL 2 dependent.

Animals↗
PubMed1989

Induction of human IgE synthesis by CD4+ T cell clones. Requirement for interleukin 4 and low molecular weight B cell growth factor.

We have analyzed in detail the precise requirements for the induction of human IgE synthesis using several experimental approaches with purified B cells and well-characterized alloantigen-specific CD4+ T cell clones expressing different profiles of lymphokine secretion. Using these clones under cognate conditions in which the B cells expressed alloantigens recognized by the cloned T cells, we have confirmed that IL-4 is required for the induction of IgE synthesis, but we have clearly demonstrated that IL-4 by itself is not sufficient. With several cloned CD4+ T cell lines, including an IL-4-producing clone that could not induce IgE synthesis, and cloned T cells pretreated with cyclosporin A to inhibit lymphokine synthesis, we showed that Th cell-B cell interactions are necessary for IgE synthesis, and that low molecular weight B cell growth factor (LMW-BCGF) and IL-4, in combination, are lymphokines of major importance in the induction of IgE synthesis. Together our results indicate that optimal induction of an IgE-specific response requires the exposure of B cells to a particular complex of signals that include (a) a signal(s) involving Th-B cell interaction that primes B cells to receive additional signals from soluble lymphokines, (b) a specific B cell proliferative signal provided by LMW-BCGF, and (c) a specific B cell differentiation signal provided by IL-4.

CD4-Positive T-Lymphocytes↗
PubMed1989

Induction of antigen-specific antibody responses in primed and unprimed B cells. Functional heterogeneity among Th1 and Th2 T cell clones.

CD4+ T cells have been recently divided into two subsets. The functions of these subsets are thought to be distinct: one subset (Th1) is responsible for delayed type hypersensitivity responses and another (Th2) is primarily responsible for induction of antibody synthesis. To more precisely define the roles of both subsets in humoral immune responses, we examined the ability of a panel of nominal antigen specific Th1 and Th2 clones to induce anti-TNP specific antibody synthesis in TNP-primed or unprimed B cells. Four of nine Th1 clones induced little or no antibody synthesis with TNP-primed B cells. However, five other Th1 clones were very effective at inducing IgG anti-TNP plaque-forming cell (PFC) responses in primed B cells. One of these Th1 clones was analysed in detail and found to also provide helper function for unprimed B cells. Cognate B-T cell interaction was required for induction of both primary and secondary responses with this clone, indicating that a Th1 clone could function as a "classical" Th cell. The seven IL-4 producing Th2 clones examined were also heterogeneous in their ability to induce antibody secretion by TNP-primed B cells. Although four of the Th2 clones induced IgG and IgM anti-TNP PFC responses, two Th2 clones induced only IgM and no IgG antibody, and another clone failed to induce any anti-TNP PFC. All Th2 clones failed to induce any anti-TNP PFC. All Th2 clones produced high levels of IL-4, but "helper" Th2 clones produced significantly greater amounts of IL-5 than "non-helper" Th2 clones. These studies indicate that some IL-2- and some IL-4-producing T cell clones can induce TNP-specific antibody in cell clones can induce TNP-specific antibody in primed and unprimed B cells, and that Th1 and Th2 clones are heterogeneous in their ability to induce Ig synthesis. Therefore, although T cell clones can be classified as Th1 or Th2 types according to patterns of IL-2, IFN-gamma, or IL-4 synthesis, the functional capacity to induce antibody synthesis cannot be predicted solely by their ability to secrete these lymphokines.

Animals↗
PubMed1988

Functional heterogeneity among human inducer T cell clones.

Analysis of mouse CD4+ inducer T cells at the clonal level has established that a dichotomy among CD4+ T cell clones exists with regard to types of lymphokines secreted. Mouse T cell clones designated Th1 have been shown to secrete IL-2 and IFN-gamma, whereas T cell clones designated Th2 have been shown to produce IL-4 but not IL-2 or IFN-gamma. To determine if such a dichotomy in the helper inducer T cell subset occurred in man, we examined a panel of human CD4+ helper/inducer T cell clones for patterns of lymphokine secretion and for functional activity. We identified human T cell clones which secrete IL-4 but not IL-2 or IFN-gamma, and which appeared to correspond to murine Th2 clones. In marked contrast to murine IL-2 secreting Th1 clones which do not produce IL-4 or IFN-gamma, we observed that some human T cell clones secrete IL-2, and IFN-gamma as well as IL-4. Southern blot analysis indicated that these multi-lymphokine-secreting clones represented the progeny of a single T cell. IL-4 secretion did not always correlated with enhanced ability to induce Ig synthesis. Although one T cell clone which secreted IL-2, IL-4, and IFN-gamma could efficiently induce Ig synthesis, another expressed potent cytolytic and growth inhibitory activity for B cells, and was ineffective or inhibitory in inducing Ig synthesis. These results indicate that although the equivalent of murine Th2 type cells appears to be present in man, the simple division of T cells into a Th1 and Th2 dichotomy may not hold true for human T cells.

Adult↗
PubMed1988

Recognition by a human alloreactive T-cell clone of an HLA-DP-associated epitope on monocytes and fibroblasts but not on B cells.

We examined the ability of a panel of allospecific (N = 9) and of TT-specific (N = 15) human inducer T-cell clones to respond to antigen presented by B cells or by monocytes. With one exception all T-cell clones responded equally well to antigen presented by monocytes, by lightly irradiated (1000 rads) peripheral blood resting B cells, or by heavily irradiated (7500 rads) Epstein-Barr virus (EBV)-transformed B cells. One alloreactive human T-cell clone, Clone A1, which recognized an HLA-DP-associated antigen proliferated in response to allogeneic monocytes and gamma-interferon-treated fibroblasts but not in response to allogeneic B cells even in the presence of autologous monocytes. Nonspecific conjugate formation between B cells and Clone A1 was normal. Yet in contrast to allogeneic monocytes, allogeneic B cells failed to induce a rise in the intracellular calcium ion concentration and failed to cause interleukin 2 (IL2) receptor expression in Clone A1. Neither interleukin 1 (IL1) nor phorbol myristate acetate (PMA) reversed the inability of Clone A1 to proliferate to allogeneic B cells. The failure of allogeneic B cells to stimulate A1 was not due to their lack of expression of the HLA-DP gene product recognized by Clone A1 or to excessive sialation of this product. These results suggest that Clone A1 recognizes an epitope associated with HLA-DP which is expressed on monocytes and on gamma-interferon-treated fibroblasts but which is either absent or altered on B cells.

Adult↗
PubMed1988

Selective defect in the antibody response to Haemophilus influenzae type b in children with recurrent infections and normal serum IgG subclass levels.

We studied 15 children with recurrent infections and normal serum IgG, IgM, IgA, and IgG-subclass levels. After immunization, the geometric mean serum IgG antibody concentration to Haemophilus influenzae type b (Hib) was eightfold lower than that of age-matched control subjects (p = 0.002). The patients also had a lower geometric mean concentration of serum IgM and IgA directed to Hib, although these differences did not reach significance. However, the groups did not differ in their response to diphtheria toxoid and pneumococcal polysaccharides. To confirm these findings, an additional 11 patients were identified and immunized. The geometric mean serum IgG anti-Hib concentration for this group of patients was also significantly lower than of normal subjects (p = 0.004). We propose that the defect in the antibody response to Hib may be a marker for a poor antibody response to a variety of bacterial and viral antigens that results in an increased propensity to recurrent infections. The defect was not associated with IgG-subclass deficiency. The identification of children with selective antibody deficiency and recurrent infections is important for diagnostic and therapeutic reasons.

Adolescent↗
PubMed1987

Requirements for activation of human peripheral blood T cells by mouse monoclonal antibodies to CD3.

The present study was undertaken in an attempt to reconcile the conflicting results concerning the signals required for the activation of human resting T cells by antibodies to the T-cell receptor/CD3 complex (Ti/CD3). For this purpose we have used highly purified peripheral blood T cells, depleted of monocytes and of preactivated Ia + T cells, to the extent that they were unable to proliferate to interleukin 2 (IL-2) alone or to optimal doses of phytohemagglutinin (PHA). To further minimize the contribution of contaminating monocytes, we used the anti-CD3 mAb, Leu-4, and cells from Leu-4 nonresponder subjects, whose monocytes we show completely fail to bind the Leu-4 mAb. The parameters of T-cell activation which we measured were rises in intracellular free calcium ion [Ca2+]i, IL-2 receptor expression IL-2 production, and cell proliferation. Our results indicate that induction of proliferation of resting T cells requires at least two signals. Signal one is best delivered by multivalent anti-CD3 mAb, such as Leu-4 mAb covalently linked to Sepharose 4B (Seph-Leu-4), or with Leu-4 mAb and anti-mouse IgG. These reagents crosslink the CD3 receptor complex on the T cell, and result in a rise in intracellular [Ca2+]i, in expression of receptors for IL-2, and in proliferation upon addition of IL-2. In contrast, purified T cells exposed to soluble Leu-4 mAb do not exhibit a rise in intracellular [Ca2+]i, do not express receptors for IL-2, and do not proliferate upon addition of IL-2, indicating that the valency of anti-CD3 mAb is critical for the delivery of the first activation signal to the T cell. The essential step of crosslinking of CD3 antigens on T cells by anti-CD3 mAb is normally mediated by monocytes which have bound anti-CD3 mAbs via their Fc receptors. Monocytes from Leu-4 nonresponder subjects, which we show fail to bind Leu-4 mAb, fail to crosslink CD3 antigens on T cells, resulting in failure of T-cell activation. The second signal needed for the proliferation of T cells whose Ti/CD3 complexes are crosslinked is IL-2. IL-2 production by such T cells required a monocyte delivered signal, which must be delivered to these T cells simultaneously with the crosslinking of their Ti/CD3 antigens. This IL-2-inductive signal can be delivered by both Leu-4 nonresponder and Leu-4 responder monocytes, indicating that delivery of this IL-2 inductive signal is independent of anti-CD3 mAb binding by monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Myocardial specific creatine phosphokinase isoenzyme elevation in children with asthma treated with intravenous isoproterenol.

We retrospectively reviewed admissions that required intravenous (IV) isoproterenol in an intensive care unit setting for management of severe childhood status asthmaticus. Elevation of the cardiac-specific serum creatine phosphokinase MB (CPK-MB) isoenzyme was noted in 15 of 19 admissions. The mean peak elevation of serum CPK in those 15 admissions was 204 IU/L with a mean peak MB band of 6.05%. Nine of the 15 admissions with elevated CPK-MB level had follow-up levels measured after IV isoproterenol had been stopped. In all nine cases, the follow-up serum CPK-MB level was 0%. In six of those nine cases, follow-up serum with undetectable CPK-MB level was obtained while the patients continued to receive IV aminophylline and corticosteroids, and inhaled but not intravenous beta-adrenergic agonist medications. These observations suggest that elevated serum CPK-MB levels that may be indicative of myocardial injury are associated with IV isoproterenol therapy of severe childhood asthma. Therefore, we recommend caution along with serial monitoring of serum CPK-MB levels when IV isoproterenol is administered in the therapy of childhood asthma.

Adolescent↗