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Biomedical subjects

G Doria

Publications and source records attributed to G Doria.

At least 109 records · Page 6Linked to original sources

Enhancement of helper and suppressor T cell activities by thymosin alpha 1 injection in old mice.

A single injection of immunodeficient old (15-24 month old) BDF1 mice with 1-100 micrograms of synthetic thymosin alpha 1 (T alpha 1), a 28-amino acid residue peptide, shortly before horse erythrocyte (HRBC)-priming, enhances the helper activity of their spleen cells. Helper activity of spleen cells from uninjected or T alpha 1-injected HRBC-primed old mice was titrated by adding graded numbers of these primed cells to cultures containing a constant number of normal spleen cells from unprimed young (3-month-old) mice and the conjugate 2,4,6-trinitrophenyl (TNP)-HRBC. As evaluated from the in vitro anti-TNP antibody response, spleen cells exhibit higher helper activity when derived from T alpha 1-injected, as compared to uninjected, HRBC-primed old mice. No effect is observed when T alpha 1 is injected in young mice before HRBC-priming. Old mice were also injected with the N14 (N-terminal amino acid residues 1-14) or the C14 (C-terminal amino acid residues 15-28) synthetic fragments of the T alpha 1 molecule. Injection of T alpha 1 or the N14 fragment restores the helper activity of old mice to levels comparable to that displayed by helper cells from young mice. Conversely, injection of the C14 fragment in old mice induces only a negligible increase in helper activity of their spleen cells. T cells from HRBC-primed mice were separated by nylon wool filtration into Th1 (non-adherent) and Th2 (adherent) T cells and these cell subpopulations were assayed for helper activity. Helper activity of Th1 and Th2 cells is found to be impaired by aging when they are tested either separately or upon their recombination.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Rearrangement and expression of the alpha- and beta-chain genes of the T-cell antigen receptor in functional murine suppressor T-cell clones.

Two different antigen-specific radiation leukemia virus (RadLV)-transformed suppressor T-cell clones, LH8.105 and LA41, exhibiting anti-lysozyme and anti-acetylcholine-receptor suppressor activity, respectively, have been examined for rearrangement and expression of genes encoding the alpha and beta chains of the T-cell receptor for antigen. LH8.105 cells express the T-cell-receptor polypeptides, as shown by specific immunoprecipitation. In both cell lines, potentially functional transcripts of alpha- and beta-chain genes are detected by RNA blot analysis. These suppressor T-cell clones exhibit alpha-chain gene rearrangements, deletion of both alleles of the constant-region (C) gene segment C beta 1, and rearrangement of the two alleles of C beta 2 when analyzed by Southern blot hybridization. Restriction analysis suggests that the DNA rearrangement is beyond the second joining-region (J) minigene of the J beta 2 cluster. These results establish that at least some mouse suppressor T-cell clones, like helper and cytotoxic T lymphocytes, rearrange and transcribe the genes coding for the alpha and beta chains of the antigen-specific T-cell receptor.

Animals↗

Synthetic peptides in the analysis of the induction and regulation of delayed-type hypersensitivity to lysozyme.

T cells mediating hen egg lysozyme (HEL)-specific delayed hypersensitivity can be activated by synthetic peptides of the 1-18 amino acid residues of hen egg lysozyme. The N-terminal 1-18 peptides of hen egg (PHEL) and ring-necked pheasant lysozyme (PREL) are highly cross-reactive in the induction of T cells mediating delayed hypersensitivity. The N-terminal 1-18 peptides of hen egg and ring-necked pheasant lysozyme (PHEL and PREL) are not cross-reactive in the induction of suppressor T cells, demonstrating that phenylalanine at amino acid residue 3 is critical for the formation of an epitope recognized by T suppressor cells.

Amino Acid Sequence↗

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↗

New derivatives of pyrrolo and pyrido[2,1-b] quinazoline as antiulcer agents.

A series of 3-benzylidene-1,2,3,9-tetrahydro-9-oxopyrrolo-[2,1-b] quinazolinecarboxylic acids and 6-benzylidene-6,7,8,9-tetrahydro-11-oxo-11H-pyrido[2,1-b] quinazolinecarboxylic acid was synthesized and evaluated for their antiulcer activity by the test of inhibition of restraint ulcers in the rat, and for gastric antisecretory activity using the technique of Shay. Some compounds appear potentially useful for therapeutic application.

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↗