Search PubMed⌕ Search

Biomedical subjects

J M Chiller

Publications and source records attributed to J M Chiller.

At least 37 records · Page 2Linked to original sources
PubMed1983

Macrophage-dependent activation of antigen-specific T cells requires antigen and a soluble monokine.

Antigen-induced T cell proliferation requires T cell interaction with antigen in the context of MHC I region-compatible accessory cells. The resulting activation and proliferation of T cells involves the production and utilization of several lymphokines or interleukins. This report describes experiments wherein these events could be separated into two phases, T cell activation and T cell proliferation. The first phase was achieved by stimulating antigen-specific T cell lines with antigen-pulsed ultraviolet light-irradiated accessory cells. T cell proliferation (second phase) could then be initiated by the addition of a soluble lymphokine with the characteristics of interleukin 1 (IL 1). These effects were only observed with homologous antigen and accessory cells syngeneic to the T cells at the I-A and E/C subregion of the MHC. This report has two applications in the study of lymphocyte-lymphokine interactions. First, T cell recognition of antigen and antigen-induced T cell proliferation can be examined as physically separate events. Secondly, this system may be used as a specific and sensitive means of measuring the effects of IL 1 on T cells.

Animals↗
PubMed1983

Unresponsiveness in hapten-specific cytotoxic T lymphocytes. IV. Functional deletion of T cell subsets required for trinitrophenyl (TNP)-specific cytotoxic T cell generation after acute or chronic treatment with trinitrobenzene sulfonic acid (TNBS).

The generation of cytotoxic T cell responses requires the interaction of a network of immunocompetent cells. Within this network, a dynamic balance of positive and negative immunoregulatory cells and their products modulate the cytotoxic T cell response. We have developed protocols which shift the balance to favor negative immunoregulation and thus result in antigen-specific unresponsiveness. In this report, a variety of approaches have been utilized to examine the effects of acute and chronic tolerance protocols on specific T cell subsets, namely amplifier helper T cells and precursor cytotoxic T cells. The results to be detailed show differential effects on these T cell subsets which are related to the tolerance protocol employed and the strains of mice tested.

Animals↗
PubMed1981

Lymphocyte specificity to protein antigens. III. Capacity of low responder mice to beef cytochrome c to respond to a peptide fragment of the molecule.

Lymph node cells derived from A.TH or A.TL mice primed with beef cytochrome c show striking patterns of reactivity when assayed in vitro for antigen-induced T cell proliferation. Whereas cells from A.TH mice respond specifically to beef cytochrome c or peptides composed of amino acids 1-65 and 81-104, cells from A.TL mice respond neither to beef cytochrome c nor to peptide 1-65, but proliferate following exposure to either peptide 81-104 or to a cytochrome c hybrid molecule in which the N-terminal peptide of beef (1-65) was substituted by a similar peptide obtained from rabbit cytochrome c. Thus, T cells from mice phenotypically unresponsive to beef cytochrome may, in fact, contain populations of lymphocytes capable of responding to a unique peptide, the response to which is totally inhibited when the same fragment is presented in the sequence of the intact protein.

Animals↗
PubMed1981

A simple and effective method to assess murine delayed type hypersensitivity to proteins.

Mice sensitized with various protein antigens emulsified in complete Freund's adjuvant by a subcutaneous injection at the base of the tail exhibited both immediate and delayed type hypersensitivities 7-8 days following sensitization. Hypersensitivity was assessed by the degree of footpad swelling elicited by challenge with a heat-aggregated form of the antigen. The swelling response was specific for the antigen used for sensitization and often resulted in a near doubling of footpad thickness. Histological examination is conjunction with studies having passive transfer of serum and adoptive transfer of either T cell-enriched or T cell-depleted preparations indicated that whereas the immediate swelling response was achieved with serum, the delayed swelling response was mediated by T lymphocytes. Adoptive transfer of specific delayed type hypersensitivity was also accomplished with small numbers of lymph node T cells obtained following in vitro enrichment and propagation.

Animals↗
PubMed1981

Orally induced tolerance. Definition at the cellular level.

Several elements of the phenomenon of oral tolerance were examined. It was shown that whereas intragastric (i.g.) exposure of mice to the T-dependent antigens ovalbumin (OVA), bovine serum albumin, and human gamma globulin severely compromised the ability to respond to a subsequent challenge with the homologous antigen, i.g. treatment with T-independent antigens such as dinitrophenylated Ficoll, polyvinylpyrrolidone and bacterial lipopolysaccharide (LPS) did not induce anergy. Furthermore, mice parenterally primed to OVA were not only refractory to the induction of oral tolerance with OVA, but displayed an anamnestic response following i.g. treatment with the antigen. In a final line of investigation, it was shown that whereas mice administered OVA orally lost specific T cell functions such as the ability to (a) provide helper activity; (b) proliferate in response to antigen, and (c) mediate delayed-type hypersensitivity, such animals possessed OVA-specific functional B cells as evidenced by the ability to respond to OVA when the antigen was administered either linked to a recognizable carrier or in conjunction with LPS.

Animals↗
PubMed1979

Ability of antigen-specific helper cells to effect a class-restricted increase in total Ig-secreting cells in spleens after immunization with the antigen.

Immunization with antigens stimulates not only B lymphocytes secreting specific antibody but, in addition, results in the generation of very large numbers of splenic Ig-secreting cells which lack specificity for that antigen. The present report examined the nature of the antigens capable of eliciting this effect and the mechanisms whereby B cells could be nonspecifically activated. It is shown that the ability of T-dependent, but not T-independent antigens, to induce such increases requires the participation of T helper cells specific for the antigen so that any one antigen results in the activation of only a proportion of total B cells. Analysis of this nonspecific plaque-forming-cell response reveals that B cell activation is not random but occurs in a class-restricted manner. The magnitude of the increase and the isotype produced are shown to be characteristic of the immunizing antigen. Based on the data presented, the apparent nonspecific T-B collaboration can best be explained by invoking a second Ig-specific helper mechanism in which helper cells capable of recognizing determinants on Ig molecules, e.g. isotype or idiotype, cause the stimulation of B cells of any specificity providing they express that determinant.

Animals↗
PubMed1979

Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes.

Murine T-lymphocyte specificity was determined in a system of antigen driven in vitro T-cell proliferation using cytochrome c molecules from different species, their derived peptides and reconstituted hybrid proteins. It was observed that primed T cells could discriminate between peptide fragments which differed from each other at a single amino acid residue. These conclusions were substantiated by the pattern of cross-reactivity noted in the response of closely related cytochrome c proteins as well as when artificial hybrid molecules reconstituted by the covalent linkage of peptide fragments were analyzed. The pattern of specificity observed appeared to be haplotype (BDF1) dependent although similar conclusions about the fine specificity of T cells in the response to cytochrome c have been obtained in other strains but associated with different residues.

Amino Acid Sequence↗
PubMed1979

Maturation of the lymphoid system. I. Induction of tolerance in neonates with a T-dependent antigen that is an obligate immunogen in adults.

A/J mice displayed a striking ontogenetic difference in the capacity to respond to DNP-Ficoll, a T-independent antigen, and to aggregated human gamma-globulin (AHGG), a T-dependent antigen. Thus, whereas responses to DNP-Ficoll of 4-day-old mice were similar in magnitude to those of adult animals, responses to AHGG did not become pronounced until mice were some 30 to 40 days of age. The inability of young animals to respond to AHGG was reflective of a negative consequence of lymphocyte/antigen interaction, since such mice became specifically unresponsive to subsequent challenges with AHGG. Unresponsiveness induced by neonatal injection of AHGG lasted 50 to 60 days, in contrast to that induced by deaggregated HGG, which persisted some 100 days longer. The unresponsive state induced by injection of neonates with AHGG maintained itself upon adoptive transfer and did not appear to be linked to suppressive factors associated with either serum or lymphoid cells for its maintenance. Finally, AHGG was also shown to be capable of inducing unresponsiveness in neonatal, athymic mice. These results demonstrate that AHGG, the normally immunogenic form of HGG in adult mice, can serve as an effective tolerogen when administered into a neonatal environment.

Aging↗
PubMed1979

Maturation of the lymphoid system. II. Characterization of the cellular levels of unresponsiveness induced in neonates by a T-dependent antigen that is an obligate immunogen in adults.

It has previously shown that AHGG, a form of HGG that is highly immunogenic in euthymic adult mice, is capable of inducing specific unresponsiveness when injected into neonatal animals. This report extends this finding and indicates that such a neonatal treatment results in the induction of tolerance in T as well as B cells. Furthermore, a similar conclusion was reached regarding specific T lymphocyte function in animals treated as neonates with OVA. The ability of LPS to modulate responses of neonatal animals to AHGG or DHGG was also examined. It appeared that such mice were not susceptible to the adjuvant effects of LPS until the 4th week of life. Furthermore, LPS was incapable of inhibiting the unresponsiveness induced in mice by either DHGG or AHGG until the 3rd or 4th week of life.

Animals↗
PubMed1979

Propagation of antigen-specific T cell helper function in vitro.

Antigen-induced proliferation of primed lymph node cells was abrogated by treatment with anti-Ly 1 serum and complement (C) but not with anti-Ly 2 serum and C. Lymph node cells from animals primed to ovalbumin were activated with antigen in vitro, followed by propagation in an antigen-free supernatant fluid obtained from lectin-induced normal spleen cells. T cells processed in this manner displayed a stepwise enrichment of helper activity for antibody production as measured in a secondary hapten-carrier response. The sequential increase in antigen-specific help was paralleled by a rise in the antigen-induced proliferative response, a phenomenon whose expression was dependent on the presence of syngeneic or semi-syngeneic irradiated filler cells.

Animals↗
PubMed1978

Enterically induced immunologic tolerance. I. Induction of suppressor T lymphoyctes by intragastric administration of soluble proteins.

Specific immune unresponsiveness was induced in inbred mice (BDF1) by the administration of soluble ovalbumin (OVA) by gastric intubation. Anti-hapten (DNP) responses likewise were specifically diminished when animals were fed autologous carrier (OVA or keyhole limpet hemocyanin). Adoptive transfer of spleen cells demonstrated that the tolerant state could be maintained in irradiated recipient mice, and specific anergy could be transferred to normal recipient animals. Adoptive suppression was mediated by T lymphocytes, as demonstrated by nylon wool fractionation and susceptibility of the cells to anti-Thy 1.2 and complement. Transferred B cells had neither suppressive nor augmentative effects. Enteric administration of OVA also specifically diminished antigen-induced DNA synthesis of primed lymph node T cells, although suppressor cells were not identified in the lymph nodes per se.

Animals↗
PubMed1977

Evolution of the lymphoid system. II. Evidence for immunoglobulin determinants on all rainbow trout lymphocytes and demonstration of mixed leukocyte reaction.

Indirect fluorescent antibody analyses utilizing antiserum specific for rainbow trout serum immunoglobulin (Ig) demonstrated that essentially all rainbow trout lymphocytes from thymus, spleen, anterior kidney and peripheral blood possess either Ig determinants or structures which cross-react with those determinants found on serum Ig. Peripheral blood leukocytes from rainbow trout were found to be caple of participating in a mixed leukocyte reaction. This observation is discussed in terms of the evolution of T cell function.

Animals↗