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Biomedical subjects

J M Chiller

Publications and source records attributed to J M Chiller.

At least 55 records · Page 3Linked to original sources
PubMed1977

Suppression of immunological activities by mouse amniotic fluid.

Mouse amniotic fluid (MAF) was shown to be capable of suppressing those antibody responses observed in euthymic or athymic mouse spleen cell cultures to the T-independent antigens dinitrophenylated Ficoll (DNP-Ficoll) and trinitrophenylated lipopolysaccharide (TNP-LPS) and to the polyclonal B-cell activators LPS and purified protein derivative of tuberculin (PPD). Titration experiments demonstrated that the suppressive capacity of MAF for either LPS or DNP-Ficoll responses was maintained up to a MAF dilution of 1:120. Preincubation of spleen cells obtained from athymic mice with MAF for 8 h significantly suppressed polyclonal B-cell activation of such cells induced by LPS, although suppression was greater when MAF was present during the entire culture period. In addition, the suppressive activity that MAF demonstrated for antibody production induced by DNP-Ficoll or LPS was not lost as a result of dialysis. MAF also suppressed the secondary in vitro proliferative responses of lymph node cells sensitized to the T-dependent antigen human gamma globulin (HGG). HGG-induced proliferation of such cells appeared to be more susceptible to suppression effected by MAF than concanavalin-A-induced proliferation.

Amniotic Fluid↗
PubMed1977

Immunologic properties of bacterial lipopolysaccharide (LPS). IV. Cellular basis of the unresponsiveness of C3H/HeJ mouse spleen cells to LPS-induced mitogenesis.

Lymphoid cells obtained from the C3H/HeJ mouse strain respond abnormally to LPS in vitro, as shown by the fact that they are unable to make a mitogenic response to some LPS preparations and make only a low mitogenic response to other LPS preparations. In contrast, cells from a closely related C3H substrain, the C3H/St, are highly responsive to both types of LPS preparations. Experiments were carried out to determine the cellular basis of these genetically determined LPS response differences. This question was approached by studying the mitogenic response to LPS in cultures containing mixtures of various combinations of B cells, T cells, and macrophages from C3H/HeJ and C3H/St mice. Experiments utilizing an LPS preparation to which the C3H/HeJ is totally unresponsive (negative LPS) revealed, first, that either spleen cells, or partially purified T cells and/or macrophages obtained from C3H/St, could not restore the ability of C3H/HeJ spleen cells to respond to LPS, indicating that the C3H/HeJ is not deficient in an LPS-specific helper cell population which may be required for mitogenesis. Secondly, the addition of either spleen cells or partially purified T cells or macrophages from the C3H/HeJ to spleen cells from the C3H/St did not inhibit the mitogenic response to LPS, suggesting that the presence of suppressor cell activity is also not involved. Experiments analogous to those described, except utilizing another LPS preparation to which the C3H/HeJ is partially responsive (positive LPS), also failed to demonstrate reconstitutive or suppressive effects when C3H/HeJ and C3H/St spleen cells were admixed. The results obtained indicate that the defect in the C3H/HeJ mouse strain that limits its responsiveness to positive LPS and which renders it totally unresponsive to negative LPS appears to be an intrinsic defect in the capacity of B cells to react to the mitogenic stimulus of LPS.

Animals↗
PubMed1977

Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative response with lymph node cells from primed mice.

An in vitro assay which measures antigen-induced proliferation of primed murine lymph node cells is described. The response is mediated by T eclls since it can be obtained by using nylon wool-passed lymphocytes (less than 1% Ig+ cells) and it can be abolished by treatment with anti-Thy 1.2 and C. Furthermore, LN cells from nu/nu mice injected with antigen do not demonstrate antigen-induced proliferation in contrast to the response observed in euthymic littermate controls. Other relevant parameters of this proliferative assay include the observations that the response is highly antigen specific, can be seen as early as 4 days and as late as 60 days after in vivo priming, is restricted to the use of certain sets of LN when animals are injected subcutaneously at the base of the tail, and can be seen with LN cells from mice primed with antigen in either CFA or ICFA. The ease of the assay coupled with its specificity and quantitative dimensions provides a direct and simple method to evaluate processes involved in antigen-induced murine T lymphocyte activation.

Animals↗
PubMed1976

Immunologic properties of bacterial lipopolysaccharide (LPS). III. Genetic linkage between the in vitro mitogenic and in vivo adjuvant properties of LPS.

The mechanism was investigated underlying the activity of bacterial lipopolysaccharide (LPS) as an adjuvant of antibody formation as assessed by its capacity to modulate the induction of tolerance in mice to the antigen human Ig G (HGG) into a state of immunity to HGG. The adjuvant activity of LPS was found to be closely correlated with its ability to function as a B-cell mitogen. This correlation was revealed by an analysis of the genetic control of the mitogenic and adjuvant properties of LPS utilizing the refractory state inherent in the C3H/HeJ mouse strain to these activities of LPS. Thus, mice that were the progeny of a backcross between the nonresponder C3H/JeJ parent and the responder (C3H/HeJ X CWB) F1 hybrid were individually typed for responsiveness to LPS, as an adjuvant and as a B-cell mitogen. It was found that LPS interfered with tolerance induction to HGG in vivo only in those backcross progeny whose spleen cells were also capable of responding mitogenically to LPS in vitro, demonstrating that the adjuvant and B-cell mitogenic properties of LPS are genetically linked. In contrast, these properties were observed to segregate independently from either H-2 or heavy chain allotype loci, and were not sex linked. These results are compatible with the concepts that, in this system, (a) the cellular site of action of LPS as an adjuvant is confined to B cells, and (b) the subcellular mode of action of LPS as an adjuvant may involve the delivery of a "signal" to B cells which is a stimulus for mitogenesis.

Adjuvants, Immunologic↗
PubMed1976

Rainbow trout leukocyte culture: a simplified method.

The addition of 10% fetal bovine serum to Leibovitz's L-15 culture medium resulted in marked growth of peripheral blood leukocytes from rainbow trout, Salmo gairdneri. Culture medium without serum or with 20% homologous serum did not induce substantial growth. In contrast to what has been reported by others, oxygenation of the culture medium was found not to be required for excellent cell growth.

Animals↗
PubMed1976

Evolution of the lymphoid system. I. Evidence for lymphocyte heterogeneity in rainbow trout revealed by the organ distribution of mitogenic responses.

Leukocytes from the various lymphoid tissues of rainbow trout (RBT) were tested for their capacity to respond to the lymphocyte mitogens concanavalin A (Con A), lipopolysaccharide (LPS), and purified protein derivative of tuberculin (PPD). Thymocytes responded to Con A but not to LPS or PPD. In contrast, leukocytes from anterior kidney were stimulated with LPS but not with Con A or PPD. Cells from spleen and peripheral blood were stimulated by each mitogen. However, the degree of stimulation at optimally stimulatory concentrations of each mitogen was distinctive. The finding that the patterns of mitogenic responses of cells from each tissue were significantly different suggested that there is lymphoid heterogeneity in the RBT with a unique tissue distribution. The species source of serum utilized as a medium supplement appeared to be capable of markedly affecting mitogenesis. Thus, LPS and PPD stimulation occurred in medium supplemented with rainbow trout serum (RBTS). On the other hand, LPS and PPD stimulation was not observed in medium supplemented with fetal bovine serum (FBS), with the exception of peripheral blood leukocytes which were stimulated by LPS in culture medium supplemented with FBS. Con A stimulated leukocytes from each lymphoid tissue in medium supplemented with RBTS and, with the exception of cells from anterior kidney, also stimulated cells from each tissue in medium supplemented with FBS. The kinetic profiles of the responses of peripheral blood leukocytes to Con A, LPS, and PPD suggested that the extent as well as the time required for maximal stimulation was dependent on the dose of mitogen.

Animals↗
PubMed1975

Immunologic properties of bacterial lipopolysaccharide (LPS). II. The unresponsiveness of C3H/HeJ Mouse spleen cells to LPS-induced mitogenesis is dependent on the method used to extract LPS.

The C3H/HeJ mouse strain, previously shown to be a nonresponder to bacterial lipopolysaccharide (LPS)-induced mitogenesis in vitro, was demonstrated by the present studies to be competent to respond mitogenically to LPS, but only to LPS preparations obtained by selected extraction methods. These preparations appear to be confined to LPS isolated by mild extraction techniques, such as TCA or butanol. In contrast, those obtained by techniques utilizing phenol were only weakly stimulatory or completely nonstimulatory for spleen cells from the C3H/HeJ. All LPS preparations tested, on the other hand, were highly stimulatory for cells from another mouse strain, namely the C3H/St. The critical importance of the method of extraction of LPS on its mitogenic activity for C3H/HeJ cells was stressed by experiments in which LPS was prepared from Escherichia coli K235 using either of two procedures. In these experiments, phenol-extracted LPS, although mitogenic in the C3H/St, was completely nonstimulatory in the C3H/HeJ; whereas, butanol-extracted LPS was highly stimulatory in both strains of mice. This striking difference was attributed to a destructive effect of phenol on LPS, as demonstrated by the fact that treatment of butanol LPS with phenol resulted in a total loss of its mitogenic activity in the C3H/HeJ, but in only a partial loss in the C3H/St. In general, the mitogenic response observed with selected LPS preparations in the C3H/HeJ was quantitatively lower and more transient than that seen with the C3H/St, although qualitatively these responses appeared to be similar. This was evidenced by the observation that in both mouse strains LPS was a specific mitogen for B cells, a property which was also attributed in both strains to the same distinct structural region of the LPS molecule, that is lipid A. A preparation of LPS that failed to stimulate B cells from the C3H/HeJ nonetheless had the capacity to block activation of these B cells by a stimulatory preparation of LPS. These results strongly suggest that mitogenic stimulation of B cells by LPS is a function of the structural integrity of both the LPS molecule and putative B-cell receptors for LPS.

Animals↗
PubMed1975

Termination of aquired and natural immunological tolerance with specific complexes.

It was possible to terminate the induced unresponsive state to bovine serum albumin (BSA) and the natural unresponsive state to autologous thyroglobulin in rabbits (RTg) by immunization with complexes composed of heterologous cross-reacting antibody and the tolerated antigens. The unresponsive state was terminated in rabbits made unresponsive by neonatal injections of BSA and then 3 mo later injected with complexes composed of BSA and guinea pig antihuman serum albumin. This termination was manifested by the presence of anti-BSA plaque-forming cells. Similarly, the natural unresponsive state was terminated in adult rabbits injected with complexes between RTg and guinea pig antibovine thyroglobulin (BTg) in that thyroid lesions and circulating anti-RTg were produced. The results can be best explained by the presence of unresponsive T cells and competent B cells, where the guinea pig gamma globulin (antibody) activates T cells specific for the guinea pig gamma globulin portion of the complexes and thus permits stimulation of B cells competent to the exposed determinants of the tolerated (BSA or RTg) portion of the complexes. The detailed mechanism for the activation of B cells in tolerant animals is discussed.

Animals↗
PubMed1975

Possible cellular events in leukemia.

An immunologically unresponsive state induced in experimental animals can be modulated by a number of procedures. Such modulation can result in the termination of the unresponsive state if there exists a normal complement of immunocompetent B cells in the presence of unresponsive T cells. It is possible to bypass the T cells and activate the B cells to respond to otherwise tolerated antigens. The bypass results from supplying a second (nonspecific) signal to the B cells, which, in the presence of antigen (specific signal), permits the B cell to differentiate. The role of the T and B cells and their activation and/or inactivation in the fate of both leukemic cells and oncogenic viruses is discussed.

Adjuvants, Immunologic↗
PubMed1975

Immunologic properties of bacterial lipopolysaccharide (LPS): correlation between the mitogenic, adjuvant, and immunogenic activities.

Bacterial lipopolysaccharide (LPS) was demonstrated to have the capacity in mice to enhance the response to soluble bovine serum albumin (BSA) and to interfere with the induction of tolerance to human gamma-globulin (HGG). These adjuvant activities were shown to occur under conditions in which LPS could also function as a B cell mitogen. This positive correlation was established by utilizing two experimental situations in which LPS was non-mitogenic for spleen cells. Thus, on the one hand, it was found that LPS did not function as an adjuvant in C3H/HeJ mice, a unique strain whose spleen cells were also unresponsive to LPS-induced mitogenesis. On the other hand, in strains which did respond to LPS mitogenically, LPS failed to function as an adjuvant when it was chemically altered to reduce its in vitro mitogenic activity. A correlation was also observed between mitogenesis and the capacity of LPS to function as a specific immunogen i mice. In contrast to the sustained and prolonged plaque-forming cell response that was observed in mice whose spleen cells were also responsive to LPS-induced mitogenesis, the response was relatively transient in the C3H/HeJ strain. These results are discussed in view of the possible in vivo modes of action of LPS.

Adjuvants, Immunologic↗
PubMed1973

The ability of bacterial lipopolysaccharide to modulate the induction of unresponsiveness to a state of immunity. Cellular parameters.

Studies were performed to define the cellular parameters involved in the interference with the induction of immunologic unresponsiveness to human gamma globulin (HGG) by bacterial lipopolysaccharide (LPS). Mice which were injected with deaggregated HGG (tolerogen) and with LPS did not become tolerant to that antigen, but rather became primed to a subsequent challenge with immunogen. The ability to prime with tolerogen and LPS was also demonstrated in an adoptive transfer system. The temporal relationship between the injection of tolerogen and that of LPS was critical for priming to occur. The injection of tolerogen and LPS not only primed mice to HGG, but also resulted in a primary antibody response to HGG. The capacity of LPS to interfere with the induction of tolerance was restricted to B cells and did not affect the ability to induce unresponsiveness in T cells. The secondary response to HGG in mice primed by tolerogen and LPS was found to be T-cell independent. These observations are interpreted and discussed from the standpoint of the ability of LPS to circumvent required T-cell cooperation and to modulate to tolerogenic stimulus into an immunogenic signal.

Animals↗
PubMed1973

Termination of tolerance to human gamma globulin in mice by antigen and bacterial lipopolysaccharide (endotoxin).

Bacterial lipopolysaccharides (endotoxin) allowed the circumvention of the thymus-derived (T) cell helper function otherwise required for the antibody response in mice to human gamma globulin (HGG). In an analogous fashion, the state of tolerance to HGG, existing at a time when bone marrow-derived (B) cells had lost their unresponsiveness, could be terminated by the injection of both immunogenic HGG and endotoxin, but by neither given alone. However, no effect on tolerance to HGG could be observed when this regimen was followed at a time when B cells were tolerant. After the spontaneous recovery from tolerance in B cells, it seemed that specific priming was occurring in that population. This phenomenon was observed either by the injection of endotoxin and HGG or by the adoptive transfer of cells into irradiated hosts. These data have been discussed in the light of potential autoimmune manifestations that could theoretically follow a simultaneous gram-negative bacterial infection along with a release of self-antigen.

Animals↗
PubMed1973

Fate of antigen-binding cells in unresponsive and immune mice.

Antigen-binding cells (ABC) to the antigen human gamma globulin (HGG) were quantitated in lymphoid tissues of A/J mice at various times after the injection of deaggregated HGG (tolerogen), aggregated HGG (immunogen), or saline. The reaction of lymphoid cells with highly labeled HGG was specific to that antigen since binding could be inhibited by excess unlabeled HGG, but not by unrelated non-cross-reacting proteins. Compared with normal mice, there was a marked decrease in the numbers of ABC in the spleens of unresponsive animals evident as early as 12 h after the injection of tolerogen. A marked increase in ABC was observed in the spleens of immunogen-injected mice, beginning at 24 h and reaching a peak at 3 days. In bone marrow, no difference in the number of ABC was found among the three experimental groups until day 20, when a reduction in ABC was observed only in tolerogen-injected mice. No quantitative difference in the thymuses in the experimental groups could be determined because of the paucity of ABC displayed by normal thymus cells.

Animals↗