Search PubMed⌕ Search

Biomedical subjects

N Chiorazzi

Publications and source records attributed to N Chiorazzi.

108 records · Page 6Linked to original sources
PubMed1979

Immune function in systemic lupus erythematosus. Impairment of in vitro T-cell proliferation and in vivo antibody response to exogenous antigen.

Peripheral blood mononuclear cells from 46 systemic lupus erythematosus (SLE) patients showed reduced ability to proliferate in vitro in response to the soluble antigen, tetanus toxoid, as compared with 96 normal controls. Special studies of 27 untreated SLE patients also revealed significantly decreased blastogenic responses to tetanus toxoid. In both the total and untreated SLE populations, decreased mean tetanus antibody titers also were found as compared with the control population. However, the reduction in antibody titer and blastogenic response was not strictly parallel. A limited immunization program was initiated in low-responding volunteers from the SLE and normal populations. Three out of four SLE patients did not develop a significant blastogenic response despite increases in anti-tetanus titers after immunization, whereas all normals showed significant increases in both blastogenic and antibody responses. The accumulated evidence indicated that the unresponsiveness was the result of a defect in T-cell function. Monocyte reactivity was demonstrated to be normal, and no evidence was found for the presence of suppressor cells, inhibition by immune complexes, or increased prostaglandins to explain the defect.

Antibodies, Bacterial↗
PubMed1979

T cell helper defect in patients with chronic lymphocytic leukemia.

Purified peripheral blood T lymphocytes from normal donors were shown to help allogeneic tonsillar B cells to differentiate and secrete specific anti-SRBC antibody in vitro in a plaque-forming assay. Utilizing this system, a comparison was made between the allogeneic helper activity generated by the T cells of normal individuals and patients with various disease states. Allogeneic helper activity was absent when T lymphocytes from patients with CLL were used. Conversely, relatively normal allogeneic helper function was provided by T cells of patients with a variety of other disorders studied. Thus, a functional deficiency was identified in CLL patients in the subpopulation of regulatory T cells responsible for providing helper activity in allogeneic interactions.

B-Lymphocytes↗
PubMed1978

Induction of in vitro differentiation and immunoglobulin synthesis of human leukemic B lymphocytes.

Successful induction of in vitro differentiation and immunoglobulin synthesis of the leukemic lymphocytes was carried out in two cases of chronic lymphocytic leukemia. Few plasma cells and little specific Ig secretion were detected in the cultures of isolated leukemic B cells in either the presence or the absence of autologous T cells. Up to 30% of the leukemic B cells matured to plasma cells, and a 32-fold increase in specific Ig synthesis was observed when T cells from normal individuals were added to the cultures of these leukemic B cells. In one of the two cases, autologous T cells were able to induce greater than 50% of the leukemic B cells to differentiate further to plasma cells in the presence of pokeweed mitogen. This markedly accelerated in vitro differentiation was only achieved with leukemic cells from cases in which there was evidence of slight differentiation in vivo. No evidence could be obtained for excessive suppressor T cells in these patients. However, a T-cell defect in the generation of allogeneic effect helper factors was identified. This defect may be responsible for the reduced rate of leukemic maturation in vivo.

B-Lymphocytes↗
PubMed1978

Ia-bearing T lymphocytes in man. Their identification and role in the generation of allogeneic helper activity.

The presence of Ia-like antigens was demonstrated on a small population (2-6%) of highly purified human circulating T lymphocytes by immunofluorescence with a rabbit anti-Ia serum raised against the isolated bimolecular Ia structure. The Ia+ T lymphocytes have no surface or intracellular immunoglobulins. The expansion of this Ia+ T-cell population was encountered in certain patients. Ia antigens were also found on T blasts grown in long-term cultures with conditioned medium generated by phytohemagglutinin-stimulated lymphocytes. In addition, leukemia blasts which stained for Ia antigens and formed E rosettes were identified in the peripheral blood of two leukemic patients. This evidence further supports the existence of Ia-bearing T cells in man. The Ia+ T-lymphocyte population was shown to contain cells responsible for the generation of allogeneic helper activity. Elimination of Ia+ lymphocytes from a purified T-cell population by the anti-Ia antiserum and complement abolished its ability to help an allogeneic B-cell preparation to generate plaque-forming cells against sheep erythrocytes in vitro in the presence of the antigen.

Antigens, Surface↗
PubMed1977

Induction of a ragweed-specific allergic state in Ir-gene-restricted nonresponder mice.

Mice of the inbred strains, C57BL/6 and C57BL/10 (H-2b), are genetically incapable of developing IgE antibody responses to ragweed pollen extract (RE) or its dinitrophenylated derivative, DNP-RE. This nonresponsiveness has previously been thought to reflect the absence of a relevant H-2-linked Ir genes controlling responses of inbred mice to these antigens. However, pretreatment of H-2b mice with either low doses of ionizing X irradiation or cyclophosphamide abrogates the nonresponder status of such animals, apparently by removal of a suppressive mechanism normally inhibiting development of IgE responses to these antigens. The implications of these findings for mechanisms of genetic control of IgE antibody synthesis and the Ir-gene concept are discussed.

Animals↗
PubMed1977

Hapten-specific IgE antibody responses in mice. VII. Conversion of IgE "non-responder" strains to IgE "responders" by elimination of suppressor T cell activity.

Mice of the inbred strains SJL (H-2s) and AKR (H-2k) are "non-responders" and "low-responders," respectively, in terms of their capacity to develop antibody responses of the IgE class when immunized with conventional proteins and hapten-protein conjugates under conditions optimal for eliciting IgE responses in "high-responder" mice, such as BALB/c (H-2d), to these same antigens. For example, BALB/c mice preimmunized with ASC and then challenged 7 days later with DNP-ASC develop peak augmented primary IgE anti-DNP antibody responses of 320 PCA units, whereas SJL and AKR mice develop responses which are 16-fold and 4-fold lower, respectively. However, pretreatment of the latter two strains with appropriate doses of either x-irradiation (150 R), cyclophosphamide (100 mg/kg) or ALS (150 mul) before carrier-preimmunization strikingly enhances the magnitude of IgE antibody responses in such mice to levels as high as 64-fold above those of untreated control mice of the same strains. Evidence obtained in these experiments indicates that the capacity of such maneuvers to to convert poor IgE responders to high responder status reflects elimination of nonantigen-specific suppressor T lymphocytes which are naturally present and normally function to suppress or "dampen" the IgE antibody response in a relatively selective manner. It appears that these cells modulate IgE responses by acting at least at two distinct points: 1) The most effective activity seems to be at the level of induction of carrier-specific helper T cells; 2) A second locus of inhibitory activity is more distal in the response, either impeding helper T cell-B cell cooperative interactions or suppressing B cell differentiation and/or function directly. Taken collectively, these observations demonstrate that the state of poor responsiveness of the SJL and AKR strains for the IgE antibody class is not a reflection of a genetic inability to develop IgE responses but rather a manifestation of a genetic capability to actively inhibit IgE antibody synthesis.

Animals↗
PubMed1976

Induction if immunological tolerance to the major antigenic determinant of penicillin: a therapeutic approach to penicillin allergy.

High titered IgE, IgG, and IgM antibody responses to the major antigenic determinant of penicillin, the benzylpenicilloyl hapten, were elicited by the intraperitoneal injection of the hapten coupled to keyhole limpet hemocyanin mixed with the appropriate adjuvant. However, treatment of such mice with the benzylpenicilloyl derivatized synthetic copolymer of D-glutamic acid and D-lysine, either before or after primary immunization, resulted in significant suppression of the subsequent anti-benzylpenicilloyl antibody responses of the IgE and IgG classes, as measured at the humoral and cellular levels. The state of tolerance induced by benzylpenicili-poly(DGlu, Lys) was highly specific, of long duration, and could be induced in a manner that would be appropriate for clinical use. These results provide a direct demonstration of the potential application of the poly(DGlu, Lys) immunotherapeutic approach to penicillin allergy in humans.

Antibody Formation↗
PubMed1976

Hapten specific IgE antibody responses in mice. V. Differential resistance of IgE and IgG B lymphocytes to X-irradiation.

The studies presented in this paper were undertaken to determine whether IgE- and IgG-producing murine B lymphocytes could be distinguished by differential resistance to x-irradiation in vivo. Sensitivity or resistance of B lymphocytes to various doses of x-irradiation was monitored by measuring the production by irradiated cells of hapten-specific IgG and IgE antibody. The results indicate that both primed and unprimed IgG B lymphocytes are less radioresistant than corresponding IgE B lymphocytes. Primed IgG B lymphocytes are more radioresistant than unprimed IgG B cells whereas unprimed IgE B lymphocytes are at least as radioresistant as primed IgE B lymphocytes. The relative radioresistance of primed IgE vs IgG B cells was best demonstrated in an adoptive transfer system. Thus, exposure of ASC-primed mice to 300 R 24 hr after transfer into these mice of syngeneic, DNP-KLH-primed spleen cells led to a sustained failure to produce IgG anti-DNP antibody after challenge with DNP-ASC; under these conditions IgE anti-DNP production was not impaired. This was shown to reflect differential radioresistance of the corresponding B cell populations. In addition, exposure to x-irradiation tended to augment IgE anti-DNP antibody responses when compared to unirradiated controls. This phenomenon is thought to reflect the effects of x-irradiation on regulatory mechanisms controlling the mouse IgE response and is explored in detail in an accompanying manuscript. The results described in this paper are discussed in the light of our evidence suggesting that, in both mouse and man, IgE B lymphocytes have certain unique characteristics by which they may be distinguished from other classes of B lymphocytes.

Animals↗
PubMed1976

Hapten-specific IgE antibody responses in mice. VI. Selective enhancement of IgE antibody production by low doses of X-irradiation and by cyclophosphamide.

Exposure of BALB/c, A/J, and (BALB/c X A/J)F1 mice, which are IgE high responder animals, to total body x-irradiation ranging from 50 to 200 R resulted in a dose-dependent enhancement of the hapten-specific IgE antibody level as compared to unirradiated control mice. In contrast, anti-hapten antibody responses of the IgG class in these same animals were rarely enhanced, and when so, were of a lesser degree. This relatively selective augmentation of the IgE vs IgG antibody responses was observed in both unprimed and primed mice. By utilizing adoptive transfer systems, it was demonstrated that the enhancing effects of x-irradiation resulted from its action on the carrier-primed cell population and not upon the responding B cells or upon macrophages. The data presented herein suggest that this enhancement phenomenon is the result of the elimination of T cells (or their products) with suppressive functions and that these cells are neither dependent upon nor specific for the carrier antigen employed in the immunization. This hypothesis is given indirect support by the observations that treatment of the same strains of mice with cyclophosphamide, in doses known to abrogate suppressive T cell functions, resulted in a similar enhancing effect to that observed after low doses of x-irradiation. In addition an interesting difference between IgE and IgG precursor B lymphocytes was observed by the ability of IgE B cells to differentiate to the secretory state at a strikingly more rapid rate than IgG B lymphocytes when exposed to comparable T cell helper influences. These observations may provide important clues to the cellular mechanisms of the immune regulation of the IgE response and its relationship to allergic diseases.

Animals↗
PubMed1976

Cell interactions between histoincompatible T an B lymphocytes. IX. The failure of histoincompatible cells is not due to suppression and cannot be circumvented by carrier-priming T cells with allogeneic macrophages.

Two possible explanations for the failure of primed histoincompatible T and B lymphocytes to cooperate in secondary responses of the IgG antibody class have been investigated in the present study: 1) The possible existence of subtle suppressive mechanisms developing as a consequence of mixing two histoincompatible cell populations; and 2) The possible inability of histoincompatible carrier-primed T cells to recognize and/or be induced to function by carrier determinants presented to them in association with foreign MHC antigens (i.e., the "altered-self" recognition hypothesis). Absence of suppression has been verified by two different approaches, including: 1) the failure of histoincompatible T cells, even in great excess, to interfere with physiologic cooperation between syngeneic T and B lymphocytes; and 2) the failure of histoincompatible B cells to interfere with physiologic cooperation between semi-syngeneic F1 hybrid T cells and parental B cells. The unlikelihood of the "altered-self" explanation for failure of histoincompatible T and B cells to cooperate has been incicated by an inability to circumvent the requirement for I-region identity by priming T cells with allogeneic macrophagebound antigen even when the latter cells are of identical haploytpe with the allogeneic B cells employed in the final cooperation assay. These results strongly substantiate the existence of true genetic restrictions in T-B cell intractions in secondary responses to hapten-protein conjugates. The validity of other observations indicating an absence of genetic restrictions in certain circumstances, considered in the context of our own data, has suggested the possibility that virgin T and B lymphocytes reciprocally influence one another during the course of cell interactions in response to antigenic and/or other signals, a process we term "adaptive differentiation."

Animals↗
PubMedDate not supplied

Identification of HSP-60 as the specific antigen of IgM produced by BRG-lymphoma cells.

In previous studies we described a patient with Burkitt's lymphoma and AIDS, whose cells recognized a molecule expressed by normal and malignant breast cells. In the present study, we identified this antigen by two-dimensional (2-D) electrophoresis and Western blotting using the antibody produced by lymphoma cells. The antigen so identified consisted of two clusters of spots with a molecular mass (Mr) of 60 and 50 kDa, respectively. Preparative immobilized pH gradient (IPG) was subsequently used to isolate the clusters of spots of higher molecular masses, from which peptide fragments of approximately 10 aa were separated on reverse-phase chromatography and sequenced. This procedure enabled the identification of the antigen recognized by the lymphoma cells as HSP-60. By means of serological analyses it was possible to identify the lower molecular mass cluster of spots as a molecule related to HSP-60. It is hypothesized that this molecule is a membrane form of HSP-60 that differs from HSP-60 in a COOH terminal portion.

Amino Acid Sequence↗