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Biomedical subjects

L Adorini

Publications and source records attributed to L Adorini.

At least 163 records · Page 9Linked to original sources

Enhancing effect of IFN-gamma on helper T cell activity and IL 2 production.

A single injection of young murine immune interferon (IFN-gamma) in young (3 mo) or old (14 to 24 mo) mice 3 days before carrier-priming significantly enhances helper T cell activity of their spleen cells. Maximal enhancement is attained when IFN-gamma is injected once immediately before priming or for 4 consecutive days from the time of priming. Helper activity for anti-TNP antibody response was titrated in vitro by adding graded numbers of spleen cells from HRBC-primed mice of a given age to cultures containing a constant number of spleen cells from 3-mo-old normal mice and TNP-HRBC. When T cell-enriched spleen cells from HRBC-primed young or old mice, uninjected or injected with IFN-gamma, were separated by nylon wool filtration into passed (Thi) and adherent (Th2) cells, the helper activity of both T cell subpopulations was found to be enhanced by IFN-gamma injection. Helper activity of purified Th1 and Th2 cells was also increased by their in vitro preincubation with IFN-gamma. Furthermore, interleukin 2 (IL 2) production by mitogen-activated spleen cells from young and old mice is enhanced by addition of IFN-gamma to cultures. These data altogether indicate that IFN-gamma plays an important role in immunoregulation of helper T cell activity.

Adjuvants, Immunologic↗

Spontaneous lymphomas in mice genetically selected for high or low phytohemagglutinin responsiveness.

Biozzi mice selected for high (Hi) or low (Lo) responsiveness to phytohemagglutinin (PHA) have been followed for their entire life-span to examine their pathology at death. Spontaneous lymphomas were found to exhibit higher incidence and faster development in Lo/PHA than in Hi/PHA females, whereas a similar difference between the two lines did not attain the level of statistical significance in male mice. The incidence of solid tumors was higher in Lo/PHA than in Hi/PHA males but the same in females of the two lines, yet the probability of dying from solid tumors was slightly increased in Lo/PHA mice of both sexes. All these results indicate that T-cell-mediated immunity influences mainly the spontaneous incidence of lymphomas and, to a lesser degree, the appearance of other solid tumors.

Animals↗

A highly sensitive enzyme-linked immunosorbent assay for idiotype-bearing antibodies.

A sensitive and specific immunoenzyme assay (ELISA) for quantitation of total and cross-reactive idiotype-bearing (CRI) anti-ABA antibodies is described. Total anti-ABA antibodies are directly assessed in ABA-BGG coated polyvinyl wells with enzyme-labelled rabbit anti-mouse immunoglobulins. By interpolation on a standard curve absorbance values give the concentration of anti-ABA antibodies with a sensitivity of 30 ng/ml. CRI+ antibodies are quantitated by inhibition of enzyme-labelled monoclonal CRI+ antibody binding to solid-phase coated rabbit anti-CRI immunoglobulins. The concentration of CRI+ antibodies, evaluated by interpolation on a standard inhibition curve, can be measured at the level of 10 ng/ml. This highly sensitive, rapid, specific and reproducible assay is easily used, with minor modifications, to detect specific antibodies in any idiotype system.

Animals↗

Immunoregulation of lysozyme-specific suppression. I. Induction and suppression of delayed-type hypersensitivity to hen egg-white lysozyme.

Subcutaneous immunization with hen egg-white lysozyme (HEL) in complete Freund's adjuvant induces, both in antibody responder and nonresponder mice, a classical delayed-type hypersensitivity (DTH) reaction evaluated as footpad swelling. This response can be specifically transferred to naive recipients by Lyt-1+2- T cells and passive transfer is restricted by genes mapping in or to the left of the I-A region of the H-2 complex. Fine antigenic specificity analysis shows that HEL-primed T cells mediating DTH recognize ring-necked pheasant egg-white lysozyme, a lysozyme closely related to HEL, but fail to respond to human lysozyme, differing from HEL at 40% amino acid residues. Complete cross-reactivity between native and denaturated (reduced and carboxymethylated) HEL is exhibited by T cells involved in the DTH response. Subcutaneous injection of HEL coupled to spleen cells is also able to induce antigen-specific and genetically restricted DTH responses whereas the same cells administered by i.v. or i.p. route induce predominantly suppressor T cell activation. These suppressor T cells specifically inhibit the induction phase of DTH reactivity to HEL.

Animals↗

Immunoregulation of lysozyme-specific suppression. II. Hen egg-white lysozyme-specific monoclonal suppressor T cell factor suppresses the afferent phase of delayed-type hypersensitivity and induces second-order suppressor T cells.

Culture supernatant from a monoclonal T cell lymphoma line (LH8-105) obtained by radiation leukemia virus-induced transformation of hen egg-white lysozyme (HEL)-specific suppressor T lymphocytes is able, when injected into mice, to specifically suppress the delayed-type hypersensitivity (DTH) reaction induced by HEL. The suppressor T cell factor (TsF) exhibits fine antigenic specificity since it suppresses the DTH response induced by HEL without affecting the DTH response induced by ring-necked pheasant egg-white lysozyme (REL), a lysozyme closely related to HEL. Conversely, LH8-105 TsF is able to suppress the DTH response induced by human lysozyme, distantly related to HEL but sharing a common epitope critical for induction of suppressive activity. The fine antigenic specificity of LH8-105 TsF for a restricted epitope on the HEL molecule is confirmed by binding to HEL but not to REL immunosorbents. This TsF also bears I-J determinants, as demonstrated by binding to monoclonal anti-I-J immunosorbents, and it suppresses the afferent but not the efferent phase of the DTH response to HEL. The afferent suppression is controlled by genes apparently mapping in the I-J subregion of the H-2 complex since I-J-incompatible mice are not suppressed by LH8-105 TsF injection. This inducer-type TsF induces second-order effector suppressor T cells only in HEL-primed mice indicating the primary role of antigen, in association with H-2 (I-J) products, in the afferent portion of this suppressive circuit.

Animals↗

Life-span, tumor incidence, and natural killer cell activity in mice selected for high or low antibody responsiveness.

Biozzi mice selected for high (H) or low (L) antibody responsiveness to natural antigens have been followed for their entire life-span to examine their pathology at death. As previously found in selection I, shorter life-span and higher lymphoma incidence were observed in L responder mice than in H responder mice selected for antibody responsiveness to sheep red blood cells (selection II). In mice selected for antibody responsiveness to Salmonella flagellar antigens (selection III), similar life-span and similar lymphoma incidence were found in H and L responder mice. Natural killer (NK) cell activity, as assessed in spleen cells from young mice, was lower in L than in H responder mice of selection I but higher in L than in H responder mice of both selections II and III. All these results indicate that longevity and lymphoma incidence at death are independent of NK cell activity in mice selected for H or L antibody responsiveness to natural antigens. Furthermore, genetic selection for antibody responsiveness does not always appear to influence life-span and lymphoma incidence.

Animals↗

Two distinct azobenzenearsonate-specific helper T-cell subpopulations mediate different forms of T-B cooperation.

Popliteal lymph node T cells from mice footpad-primed with azobenzenearsonate (ABA)-protein conjugates were able to help the anti-trinitrophenyl (TNP) and anti-ABA plaque-forming cell (PFC) responses of normal syngeneic spleen cells cultured in vitro with TNP-ABA-keyhole limpet haemocyanin. Enrichment in ABA-specific helper cells was obtained by positive selection of ABA-primed T cells on ABA-pulsed syngeneic macrophages. The ABA-specific T cells induced by ABA-protein priming are able to help the anti-TNP PFC response of normal B cells through recognition of the ABA determinant either unlinked to TNP (ABA and TNP separately presented to T and B cells) or linked to TNP (ABA and TNP presented as moieties of the same molecule). These two mechanisms of T-B cooperation are mediated by two different ABA-specific helper T-cell subpopulations, which can be distinguished by their different radiosensitivities: the former mechanism is mediated by radioresistant T cells, whereas the latter is mediated by radiosensitive T cells. Both helper T-cell subpopulations bind the ABA-pulsed syngeneic macrophages, demonstrating the presence of ABA-specific receptors on both cell types.

Animals↗

Fine antigenic specificity and genetic restriction of lysozyme-specific suppressor T cell factor produced by radiation leukemia virus-transformed suppressor T cells.

Culture supernatants obtained from a radiation leukemia virus-transformed, hen egg-white lysozyme (HEL)-specific, suppressor T cell line are able, when injected into mice, to specifically suppress the anti-HEL antibody response. Suppression is observed on both primary and secondary anti-HEL antibody responses evaluated by direct and developed hemolytic plaque assays. Culture supernatants from this HEL-specific suppressor T cell line do not suppress the antibody response induced by a structurally related lysozyme, demonstrating the presence in the culture supernatant of a suppressor factor endowed with fine antigenic specificity. The suppressor factor is able to selectively suppress the anti-HEL antibody response induced by the N-terminal C-terminal peptide of the HEL molecule indicating that the fine specificity of this factor is restricted to an antigenic epitope present in this region of the HEL molecule. The suppressive activity is restricted by genes located within the H-2 complex and analysis of the suppression induced in recombinant mice demonstrates that the interaction between HEL-specific suppressor T cell factor and its cellular target requires identity in the I-J region of the H-2 complex.

Animals↗

Immunoregulation in senescence: increased inducibility of antigen-specific suppressor T cells and loss of cell sensitivity to immunosuppression in aging mice.

Azobenzenearsonate (ABA)-specific T cell-mediated suppression has been studied in aging mice. ABA-specific suppressor T cells were induced in young and old mice by injection of ABA conjugated to syngeneic spleen cells (ABA-SC). These suppressor cells were tested for their ability to suppress the in vitro anti-trinitrophenyl (TNP) antibody response of lymph node cells obtained from ABA-keyhole limpet hemocyanin (KLH)-primed young or old mice and cultured with TNP-ABA-KLH. Suppressor T cells were found to be more easily induced in old than in young mice but to suppress less efficiently the antibody response of cells from old than from young mice. The increased inducibility of antigen-specific suppressor T cells in old mice is compatible with the age-dependent decline of immune responsiveness to exogenous antigens. The loss of cell sensitivity to antigen-specific immunosuppression as well as the lack of evidence for increased nonspecific suppression in old mice is consistent with the age-related increase in autoimmune disorders. These findings provide a unifying explanation for the most relevant immunological phenomena of senescence.

Aging↗

Production of antigen-specific suppressive T cell factor by radiation leukemia virus-transformed suppressor T cells.

Hen egg-white lysozyme (HEL)-specific suppressor T cells induced in C57BL/6 mice have been selected by sequential passage over plates coated with goat anti-mouse Ig and HEL. These suppressor T cells, 80% I-J+, were infected in vitro with radiation leukemia virus (RadLV/Nu1) and injected intravenously into sublethally irradiated syngeneic recipients. After 4-6 months, 6 out of 20 injected mice developed thymic lymphomas, which were maintained by transplantation into histocompatible hosts and subsequently established as permanent cell lines. Cells of these six thymomas were screened for the presence of Thy 1.2, Lyt 1, Lyt 2, I-Jb, and Ig cell surface antigens by direct or indirect immunofluorescence. One tumor (thymoma L4) was found to express the expected phenotype of suppressor T cells (Thy 1.2+, Lyt 2+, I-J+). High-speed supernatants of extracts obtained from L4 cells were able to induce HEL-specific suppression in a T cell proliferative assay, demonstrating the presence of an antigen-specific suppressive T cell factor.

Animals↗

Differential major histocompatibility complex-related activation of idiotypic suppressor T cells. Suppressor T cells cross-reactive to two distantly related lysozymes are not induced by one of them.

B10 (H-2b) mice are genetic nonresponders to hen egg-white lysozyme (HEL) and the distantly related human lysozyme (HUL). However, anti-HEL or anti-HUL primary antibody responses in vivo or in vitro can be obtained in B10 mice by immunization with the appropriate lysozyme coupled to erythrocytes. T cells able to suppress either anti-lysozyme plaque-forming cells (PFC) response are induced in B10 mice after immunization with HEL-complete Freund's adjuvant (CFA) or HUL-CFA. This cross-reactivity of HEL and HUL in the induction and the expression of suppressive activity is in marked contrast to their very low cross-reactivity at the PFC level. These results suggest that either HEL or HUL can stimulate a suppressor T cell which recognizes a particular epitope present on both lysozymes. Suppressor cells induced by HEL or HUL bear the same predominant idiotype found on the majority of anti-HEL antibodies, and on the small proportion of anti-HUL antibodies cross-reactive with HEL. B10.Q (H-2q) mice are responders in vivo to HEL-CFA, but not to HUL-CFA. In contrast to B10, HEL-CFA priming in B10.Q micr induces helper cells whereas HUL-CFA priming induces suppressor cells. These suppressor cells are cross-reactive with HEL and are fully able to suppress HEL-specific helper cells. The presence of HEL-specific suppressor cell precursors in B10.Q mice which are not activated by HEL, seems to implicate differential choice by the antigen presenting system as a basis for Ir gene control, rather than the absence of a regulatory cell type from the T cell repertoire.

Animals↗

Lysozyme-induced T-suppressor cells and antibodies have a predominant idiotype.

The existence of shared idiotypic determinants on the surfaces of T and B cells is now firmly established, suggesting that on both these cell types immunoglobulin variable regions are expressed which presumably function as antigen receptors. In most systems this has been inferred through the use of anti-idiotypic antibody instead of antigen to induce either helper or suppressor T cells. Recent evidence demonstrates that antigen-specific suppressor or helper factors can also bear idiotypic determinants. It is possible that these factors represent released receptors or portions of receptors. We show here the direct elimination of an antigen-induced T-suppressor population by an anti-idiotypic serum and complement. These suppressor T cells as well as the idiotypic population used to generate the antiserum are each specific for the same limited portion of the multi-determinant antigen, lysozyme. Apparently, these suppressor cells are restricted in specificity as well as share idiotypy with antibodies of the same specificity.

Animals↗

Fine specificity of regulatory T cells. II. Suppressor and helper T cells are induced by different regions of hen egg-white lysozyme in a genetically nonresponder mouse strain.

We have examined the ability of two purified peptide fragments derived from hen (chicken) egg-white lysozyme (HEL); N-terminal, Co-terminal peptide (a.a. 1--17:cys 6--cys 127:120--129) and mixed disulfide LII peptide (LII) (a.a. 13--105) to induce antigen-specific suppression or help in B10 (H-2b) nonresponder and B10.A (H-2a) responder mice. An anti-HEL primary in vitro antibody response can be obtained in either strain by stimulation with HEL coupled to erythrocytes (RBC). Preimmunization with HEL-complete Freund's adjuvant-(CFA) or N-C-CFA-induced suppression of the anti-HEL PFC response to HEL-RBC in spleen cell cultures from B10 mice, whereas helper activity was demonstrated in cultures from B10.A mice similarly immunized. LII-CFA priming elicited helper cells in both C57BL/10 Sn (B10) and B10.A/SgSn (B10.A) mice. The genetic nonresponsiveness of B10 mice to HEL can therefore be attributed to the activation of suppressor T cells by a limited portion of the molecule (e.g., N-C) which prevent the potential response directed against other epitopes on the same molecule (e.g., LII). One manifestation of major histocompatibility complex gene activity appears to be the intramolecular selection of different antigenic determinants leading to activation of functionally different T-cell subpopulations.

Amino Acid Sequence↗