scholarly journals Regulatory mechanisms in cell-mediated immune responses. II. A genetically restricted suppressor of mixed lymphocyte reactions released by alloantigen-activated spleen cells.

1975 ◽  
Vol 142 (6) ◽  
pp. 1391-1402 ◽  
Author(s):  
S S Rich ◽  
R R Rich
Keyword(s):  
Immune Responses ◽  
Mixed Lymphocyte Reaction ◽  
Antigenic Specificity ◽  
Spleen Cells ◽  
Suppressor Factor ◽  
Homology Relationship ◽  
Cell Suppression ◽  
Mixed Lymphocyte Reactions

The mechanism of alloantigen-activated spleen cell suppression of mixed lymphocyte reaction (MLR) is explored in this report. Activated murine suppressor spleen cells elaborated a soluble noncytotoxic factor which suppressed MLR responses by 55-95%. Generation of suppressor factor required both in vivo alloantigen sensitization and specific in vitro restimulation. Suppressor factor was not produced by activated spleen cells which had been treated with anti-Thy-1.2 serum and complement. Antigenic specificity toward alloantigens of the stimulator cells was not demonstrable. In contrast, suppressor factor effectively inhibited MLR response only of responder cells of those strains that shared the D-end and the I-C subregion of the H-2 complex with the cells producing suppressor factor. Therefore, active suppression appears to require an MHC-directed homology relationship between regulating and responder cells in MLR.

scholarly journals Regulatory mechanisms in cell-mediated immune responses. V. H-2 homology requirements for the production of a minor locus-induced suppressor factor.

1977 ◽  
Vol 146 (4) ◽  
pp. 1152-1157 ◽  
Author(s):  
D L Kastner ◽  
R R Rich ◽  
L Chu ◽  
S S Rich
Keyword(s):  
Major Histocompatibility Complex ◽  
Immune Responses ◽  
Regulatory Mechanisms ◽  
Mixed Leukocyte Reaction ◽  
Spleen Cells ◽  
Suppressor Factor ◽  
Histocompatibility Complex ◽  
A Minor

A mixed leukocyte reaction suppressor factor is produced by spleen cells sensitized in vivo and restimulated in vitro across non-H-2 antigenic barriers. Cells capable of producing this factor appear in the spleens of minor locus-immunized animals later than in animals sensitized to major histocompatibility complex-encoded antigens. However, both H-2 and non H-2-induced factors suppress proliferative responses to any alloantigen. Splenocytes from animals immunized with H-2-identical, minor locus-disparate cells produce suppressor factor in vitro only when restimulated with cells sharing both H-2 and non-H-2 antigens with the in vivo stimulators.

scholarly journals GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO

1974 ◽  
Vol 140 (3) ◽  
pp. 648-659 ◽  
Author(s):  
Judith A. Kapp ◽  
Carl W. Pierce ◽  
Stuart Schlossman ◽  
Baruj Benacerraf
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cell Function ◽  
Suppressor Cells ◽  
Specific Response ◽  
Spleen Cells ◽  
X Irradiation

In recent studies we have found that GAT not only fails to elicit a GAT-specific response in nonresponder mice but also specifically decreases the ability of nonresponder mice to develop a GAT-specific PFC response to a subsequent challenge with GAT bound to the immunogenic carrier, MBSA. Studies presented in this paper demonstrate that B cells from nonresponder, DBA/1 mice rendered unresponsive by GAT in vivo can respond in vitro to GAT-MBSA if exogenous, carrier-primed T cells are added to the cultures. The unresponsiveness was shown to be the result of impaired carrier-specific helper T-cell function in the spleen cells of GAT-primed mice. Spleen cells from GAT-primed mice specifically suppressed the GAT-specific PFC response of spleen cells from normal DBA/1 mice incubated with GAT-MBSA. This suppression was prevented by pretreatment of GAT-primed spleen cells with anti-θ serum plus C or X irradiation. Identification of the suppressor cells as T cells was confirmed by the demonstration that suppressor cells were confined to the fraction of the column-purified lymphocytes which contained θ-positive cells and a few non-Ig-bearing cells. The significance of these data to our understanding of Ir-gene regulation of the immune response is discussed.

scholarly journals Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. II. T lymphocyte-mediated cytolysis.

1980 ◽  
Vol 152 (5) ◽  
pp. 1184-1193 ◽  
Author(s):  
T Boon ◽  
J Van Snick ◽  
A Van Pel ◽  
C Uyttenhove ◽  
M Marchand
Keyword(s):  
Tumor Cell ◽  
T Lymphocyte ◽  
Peritoneal Exudate ◽  
Antigenic Specificity ◽  
Spleen Cells ◽  
Peritoneal Exudate Cells ◽  
Specific Antigens

Tumor cell variants that were rejected by syngeneic mice (tum-) were obtained from mastocytoma P815 by mutagenesis (as described in the accompanying report (13). A considerable T lymphocyte-mediated lysis was observed upon incubation of these tum- variants with peritoneal exudate cells collected a few days after an intraperitoneal challenge of immune animals. Spleen cells from these animals were cytolytic after stimulation in vitro with the immunizing variant. New antigens, absent from the original P815 tum+ cells, were detected on 15 of the 21 tum- variants that were tested. All these antigens appeared to be different. No new antigen was detected on any of 10 mutagenized P815 clones that had retained their ability to form tumors. We compared the evidence obtained in vivo and in vitro for the presence of specific antigens on five tum- variants. Three variants were shown both in vivo and in vitro to carry an individual antigen. One showed no specificity either in vivo or in vitro. However, for one variant, no specificity was observed in vivo, although cytolysis tests demonstrated the existence of a singular antigenic specificity.

Parasitology and immunology of mice vaccinated with irradiated Litomosoides sigmodontis larvae

Parasitology ◽  
2000 ◽  
Vol 120 (3) ◽  
pp. 271-280 ◽  
Author(s):  
L. LE GOFF ◽  
C. MARTIN ◽  
I. P. OSWALD ◽  
P. N. VUONG ◽  
G. PETIT ◽  
...  
Keyword(s):  
Immune Responses ◽  
Recovery Rate ◽  
Spleen Cells ◽  
Challenge Inoculation ◽  
Infective Larvae ◽  
Litomosoides Sigmodontis ◽  
Before And After ◽  
Type Response

This study was performed with Litomosoides sigmodontis, the only filarial species which can develop from the infective larvae to the patent phase in immunocompetent laboratory BALB/c mice. Parasitological features and immune responses were analysed up to 3 months before and after challenge inoculation, by comparing 4 groups of mice: vaccinated challenged, challenged only, vaccinated only, and naive mice. Male larvae were very susceptible to irradiation and only female irradiated larvae survived in vivo. Protection, assessed by a lower recovery rate, was confirmed and was established within the first 2 days of challenge. This early reduction of the recovery rate in vaccinated challenged mice was determined by their immune status prior to the challenge inoculation. This was characterized by high specific IgM and IgG subclass (IgG1, IgG2a and IgG3) levels, high specific IL-5 secretion from spleen cells in vitro and a high density of eosinophils in the subcutaneous connective tissue. Six h after the challenge inoculation, most tissue eosinophils were degranulated in vaccinated challenged mice. Thus, in the protocol of vaccination described, protection appeared mainly to result from the stimulation of a Th2 type response and eosinophils seemed to be the main effectors for the increased killing of infective larvae in vaccinated challenged mice. Two months after challenge inoculation, the percentage of microfilaraemic mice was lower in vaccinated challenged mice as a consequence of this overall reduction in the worm load. In both vaccinated challenged and challenged only groups, the in vitro splenocyte proliferative capacity was reduced in microfilaraemic mice.

scholarly journals Suppressor T cells activated in a primary in vitro response to non-major histocompatibility alloantigens.

1982 ◽  
Vol 156 (5) ◽  
pp. 1398-1414 ◽  
Author(s):  
S Macphail ◽  
O Stutman
Keyword(s):  
Mixed Lymphocyte Reaction ◽  
Cytotoxic T Lymphocyte ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Normal Spleen ◽  
In Vitro Response

Normal mouse spleen cells are not capable of mounting a primary cytotoxic T lymphocyte (Tc) response to non-H-2 alloantigens in vitro, although a good secondary H-2-restricted response is observable after in vivo immunization of the responder animals. Suppressor cells are generated in such a primary responses provided a Mls incompatibility exists between the responder and stimulator. These suppressors are not antigen specific, are Thy-1+, Lyt-1+, 2-, I-J-, and are highly radiosensitive. The suppressor cell precursors in normal spleen express the same phenotype. These suppressor cells are probably implicated in the lack of a primary Tc response in a primary mixed lymphocyte reaction across non-H-2 incompatibilities that include an Mls difference.

scholarly journals GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO

1974 ◽  
Vol 140 (1) ◽  
pp. 172-184 ◽  
Author(s):  
Judith A. Kapp ◽  
Carl W. Pierce ◽  
Baruj Benacerraf
Keyword(s):  
Immune Response ◽  
Gene Regulation ◽  
B Cells ◽  
Bovine Serum Albumin ◽  
Immune Responses ◽  
Bovine Serum ◽  
Tolerance Induction ◽  
Spleen Cells

Although nonresponder, H-2s and H-2q, mice fail to develop GAT-specific PFC responses to GAT, they do develop GAT-specific PFC responses when stimulated by GAT complexed to an immunogenic carrier such as methylated bovine serum albumin. The studies described in this paper show that injection of nonresponder mice with GAT specifically decreases their ability to develop anti-GAT PFC responses to a subsequent challenge with GAT-MBSA. Addition of GAT to cultures of spleen cells from nonresponder mice also prevents development of the GAT-specific PFC responses stimulated by GAT-MBSA. Thus, interaction of nonresponder spleen cells with GAT leads to the induction of unresponsiveness in vivo and in vitro. Various parameters of the tolerance induction have been investigated and described. A comparison of the effects of GAT on B cells indicates that nonresponder B cells are more readily rendered unresponsive by soluble GAT than are responder B cells. The significance of these data for our understanding of Ir gene regulation of the immune response is discussed.

scholarly journals GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO

1973 ◽  
Vol 138 (5) ◽  
pp. 1107-1120 ◽  
Author(s):  
Judith A. Kapp ◽  
Carl W. Pierce ◽  
Baruj Benacerraf
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Plaque Assay ◽  
Immune Response Gene ◽  
Spleen Cells ◽  
Response Gene ◽  
In Vitro System ◽  
Cellular Events

In vivo, the antibody response in mice to the random terpolymer L-glutamic acid50-L-alanine30-L-tyrosine10 (GAT) is controlled by a histocompatibility-linked immune response gene(s). We have studied antibody responses by spleen cells from responder and nonresponder mice to GAT and GAT complexed to methylated bovine serum albumin (GAT-MBSA) in vitro. Cells producing antibodies specific for GAT were enumerated in a modified Jerne plaque assay using GAT coupled to sheep erythrocytes as indicator cells. Soluble GAT stimulated development of IgG GAT-specific plaque-forming cell (PFC) responses in cultures of spleen cells from responder mice, C57Bl/6 (H-2b), F1 (C57 x SJL) (H-2b/s), and A/J (H-2a). Soluble GAT did not stimulate development of GAT-specific PFC responses in cultures of spleen cells from nonresponder mice, SJL (H-2s), B10.S (H-2s), and A.SW (H-2s). GAT-MBSA stimulated development of IgG GAT-specific PFC responses in cultures of spleen cells from both responder and nonresponder strains of mice. These data correlate precisely with data obtained by measuring the in vivo responses of responder and nonresponder strains of mice to GAT and GAT-MBSA by serological techniques. Therefore, this in vitro system can effectively be used as a model to study the cellular events regulated by histocompatibility-linked immune response genes.

scholarly journals INDUCTION OF IMMUNOLOGICAL TOLERANCE TO A THYMUS-DEPENDENT ANTIGEN IN THE ABSENCE OF THYMUS-DERIVED CELLS

1974 ◽  
Vol 139 (5) ◽  
pp. 1303-1316 ◽  
Author(s):  
John W. Schrader
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
Cell Function ◽  
Immunological Tolerance ◽  
Athymic Mice ◽  
Spleen Cells ◽  
Amplifying Effect ◽  
Bone Marrow Derived Cells

Specific immunological unresponsiveness was induced using thymus-dependent antigens in congenitally athymic (nu/nu) mice, in which no T-cell function has been demonstrated. The tolerance was induced in vivo by the injection of 5–10 mg of either FGG or DNP-HGG. Spleen cells from treated mice were tested in vitro for the ability to mount thymus-independent immune responses against FGG in the presence of polymerized flagellin POL, and the DNP determinant conjugated to POL. A specific deficiency in either the in vitro anti-FGG or anti-DNP response was demonstrated, depending on the antigen used for treatment of the spleen cell donor. Athymic mice treated with FGG were also tested by in vivo challenge with FGG given with POL as an adjuvant and were found to be hyporesponsive. Unresponsiveness to in vitro challenge was established by 24 h after the in vivo injection of FGG. It was found that the injection of POL with the FGG prevented the development of unresponsiveness, but not if the POL was given 24 h or more after the FGG. The unresponsiveness could not be overcome by confrontation with allogeneic spleen cells from CBA mice, although the presence of allogeneic spleen cells had a large amplifying effect on the response of control spleen cells. These experiments demonstrate a mechanism for the tolerization of bone marrow-derived cells by thymus-dependent antigens in the absence of the thymus.

scholarly journals ACTIVE SUPPRESSION AS A POSSIBLE MECHANISM OF TOLERANCE IN TETRAPARENTAL MICE

1973 ◽  
Vol 137 (2) ◽  
pp. 291-300 ◽  
Author(s):  
S. Michael Phillips ◽  
Thomas G. Wegmann
Keyword(s):  
Experimental System ◽  
Cell Types ◽  
Parental Cell ◽  
Spleen Cells ◽  
Cell Stage ◽  
Self Tolerance ◽  
Blocking Antibodies ◽  
Mixed Lymphocyte Reactions

Previous work has indicated that tetraparental mice, chimeric since the eight-cell stage because of embryo fusion using histoincompatible strain combinations, possess autospecific immune cells and blocking antibodies. Although this phenomenon has been demonstrated in vitro, it may have relevance to the self-tolerance shown by these mice in vivo. The experiments described here indicate that spleen cells from tetraparental mice can block mixed lymphocyte reactions between the two parental cell types, but not between unrelated strains. Furthermore, this suppressive ability is not affected by an otherwise effective treatment of the tetraparental spleen cells with anti-θ antibody and complement. The in vitro experimental system elaborated here should help to characterize the cell type responsible for the suppression.

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