scholarly journals Cell interactions in the suppression of in vitro antibody responses.

1976 ◽  
Vol 143 (6) ◽  
pp. 1421-1428 ◽  
Author(s):  
C E Calkins ◽  
S Orbach-Arbouys ◽  
O Stutman ◽  
R K Gershon

Normal T and immune B lymphocytes interact in a fashion that leads to suppression of the immune response. Normal spleen cells added to cultures of primed spleen cells specifically suppressed both the IgM and IgG secondary antibody response of the primed cells to less than 30% of the response of the immune cells cultured alone. Cell crowding as a possible in vitro artifact was ruled out. The suppression was specific for the priming antigen, even when the specific and nonspecific antigens were included in the same cultures. Suppression required both normal T and immune B cells to be present in culture. We suggest that the immune population produces a signal that can induce normal T cells to become specific suppressor cells. This form of interaction may represent an important regulatory (homeostatic) mechanism in the immune system.

1973 ◽  
Vol 137 (2) ◽  
pp. 369-386 ◽  
Author(s):  
James Forman ◽  
Sven Britton

The cytotoxic effect of spleen cells from H-2 allogeneic mice was tested in vitro against an A strain leukemia (YAC) labeled with [125I]iododeoxyuridine. After the mice were primed with tumor cells, significant and specific H-2 immunity was detected on day 3 and peak cytotoxicity was observed between 7 and 14 days after priming. Two effector cells appear to be involved in the host response, because spleens taken from mice soon after priming were not sensitive to antitheta sera and complement while those taken during the peak stages of the response showed a marked reduction in cytotoxicity after treatment. Macrophages were not involved, since removal of these cells by the carbonyl iron method did not result in any reduction in cytotoxicity. Immune serum that was capable of inducing cell-mediated cytotoxicity in normal spleen cell populations also augmented cytotoxicity of spleen cells taken from mice primed 3 days previously. However, when spleen cells were taken from mice during the peak phase of the immune response, the same serum at the same dilutions inhibited the preexisting cytotoxicity. A difference was also detected in the killing efficiencies between early and late immune cells.


1982 ◽  
Vol 156 (5) ◽  
pp. 1398-1414 ◽  
Author(s):  
S Macphail ◽  
O Stutman

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.


1976 ◽  
Vol 144 (2) ◽  
pp. 371-381 ◽  
Author(s):  
C W Pierce ◽  
J A Kapp ◽  
B Benacerraf

The ability of antigen-bearing syngeneic and allogeneic peptone-induced peritoneal exudate macrophages to support development of primary and secondary antibody responses by murine lymphoid or spleen cells in vitro has been investigated. The antigen used was the terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). Syngeneic and allogeneic macrophages supported development of comparable primary antibody responses to GAT, indicating that genetic restrictions do not limit efficient macrophage-lymphocyte interactions in primary responses. By contrast, immunized spleen or lymphoid cells developed secondary antibody responses preferentially when stimulated in vitro with GAT on macrophages syngeneic to the macrophages used to present GAT during in vivo immunization. Thus, genetic restrictions regulate efficient macrophage-lymphocyte interactions in secondary antibody responses. These restrictions have been demonstrated from 2 to 8 wk after a single immunization with limiting quantities of GAT and are controlled by the H-2 gene complex. The implications that immune lymphocytes selectively recognize and respond to antigen presented in the context of the macrophage membrane-antigen complex which sensitized the lymphocytes initially are considered.


1977 ◽  
Vol 146 (6) ◽  
pp. 1827-1832 ◽  
Author(s):  
C W Pierce ◽  
R N Germain ◽  
J A Kapp ◽  
B Benacerraf

The development of IgG L-glutamic Acid60-L-alanine30-L-tyrosine10 (GAT)-specific plaque-forming cell responses in vitro by virgin and immune (responder X nonresponder)F1 spleen cells after stimulation with responder and nonresponder parental GAT-macrophages (Mphi) was investigated. Virgin F1 spleen cells developed comparable primary responses to both parental GAT-Mphi. By contrast, F1 spleen cells from mice immunized with GAT or responder parental GAT-Mphi developed secondary responses after stimulation with only responder parental GAT-Mphi. Spleen cells from F1 mice immunized with nonresponder parental GAT-Mphi developed secondary responses to these GAT-Mphi, but failed to respond to responder parental GAT-Mphi. These results are discussed in the context of genetic restrictions regulating Mphi-T-cell interactions in secondary antibody responses and the possible expression of Ir-gene function in Mphi.


1974 ◽  
Vol 139 (1) ◽  
pp. 24-43 ◽  
Author(s):  
Dieter Armerding ◽  
David H. Katz

The present studies were undertaken to analyze the nature of the effect of bacterial lipopolysaccharide (LPS) on antibody production in vitro. We have done this by making comparative studies of the effects of LPS on in vitro primary and secondary antibody responses to soluble hapten-protein conjugates and to particulate and soluble sheep erythrocyte antigens. The results obtained demonstrate that the biological action of LPS in vitro may be predominantly manifested on the function of B lymphocytes or T lymphocytes depending on the conditions employed. In the absence of antigen, LPS appears to act primarily on B lymphocytes. In the presence of antigen, however, the data presented here show that LPS significantly influences specific helper T-cell function and it is this latter influence that is predominantly responsible for the adjuvant effects of LPS on antigen-specific antibody responses.


1973 ◽  
Vol 138 (1) ◽  
pp. 143-162 ◽  
Author(s):  
J. Sprent ◽  
J. F. A. P. Miller

When spleen, mesenteric lymph node, or Peyer's patch cells from mice primed 24 h before with either sheep erythrocytes (SRC) or horse erythrocytes (HRC) were transferred together with both SRC and HRC to irradiated mice, antibody responses measured 7 days later were very low to the priming antigen but high to the other antigen. This was demonstrated either by measuring numbers of antibody-forming cells in spleen or levels of hemagglutinins in serum. Specific unresponsiveness of the transferred cells was evident in both the 19S and 7S responses. It was observed only when strict experimental conditions were followed: (a) the cell donors had to be primed with not less than 109 erythrocytes given intravenously; (b) the cells had to be transferred between 1 and 2 days after antigen priming; (c) antibody responses in the recipients were measured within 7 days of cell transfer, i.e., partial recovery was evident by 11 days; (d) the transferred cells had to be challenged in the recipients within 1 day after cell transfer: when challenge was delayed for 5 days or longer, responsiveness returned. The failure of cells from recently primed donors to respond to the priming antigen on adoptive transfer could be overcome by supplementing with normal spleen cells, but not with thymus alone or bone marrow alone. This implied that unresponsiveness occurred at the levels of both T and B lymphocytes, and was not due to a suppressive influence exerted by T cells. Further work is in progress to determine the mechanism of this transient state of specific unresponsiveness.


1979 ◽  
Vol 150 (4) ◽  
pp. 898-908 ◽  
Author(s):  
K Suzuki ◽  
T B Tomasi

The primary IgM antibody response to sheep erythrocytes in vivo as well as in vitro is markedly decreased in the spleen cells of pregnant mice, compared to age-matched female controls. Decreased antibody synthesis appears to be mediated by nonspecific suppressor cells, because the addition of pregnant spleen cells to the normal spleen cell cultures causes a significant suppression of plaque-forming-cell responses of the normal spleen cells. Suppressor cell activity was not observed in lymph nodes of pregnant mice. At least two populations of pregnant spleen cells were shown to exert a suppressor cell activity; one is T lymphocytes and the other a nylon-adherent cell present in the B-cell-enriched macrophage-depleted fraction. Pregnant spleen cells cultured in vitro were shown to secrete a soluble suppressive factor(s) into the supernatant medium.


1973 ◽  
Vol 137 (6) ◽  
pp. 1311-1324 ◽  
Author(s):  
Leonore A. Herzenberg ◽  
Eva L. Chan ◽  
Myrnice M. Ravitch ◽  
Roy J. Riblet ◽  
Leonard A. Herzenberg

Thymus-derived cells (T cells) that actively suppress production of IgG2a immunoglobulins carrying the Ig-1b allotype have been found in adult (SJL x BALB/c)F1 mice exposed to anti-Ig-1b early in life. The suppression is specific for Ig-1b. The allelic product, Ig-1a, is unaffected. Spleen, lymph node, bone marrow, or thymus cells from suppressed mice suppress production of Ig-1b by syngeneic spleen cells from normal F1 mice. When a mixture of suppressed and normal cells is transferred into lethally irradiated BALB/c mice, there is a short burst of Ig-1b production after which Ig-1b levels in the recipient fall rapidly below detectability. Pretreatment of the cells from the suppressed mice with antiserum specific for T cells (anti-Thy-1b) plus complement before mixture destroys the suppressing activity. Similar results with suppressor cells were obtained in vitro using Mishell-Dutton cultures. Mixture of spleen cells from suppressed animals with sheep erythrocyte (SRBC)-primed syngeneic normal spleen before culture suppresses Ig-1b plaque-forming cell (PFC) formation while leaving Ig-1a PFC unaffected. Treatment of the suppressed spleen with anti-Thy-1b before transfer removes the suppressing activity.


1976 ◽  
Vol 144 (4) ◽  
pp. 996-1008 ◽  
Author(s):  
J R Neefe ◽  
D H Sachs

Monolayers formed of normal mouse spleen cells attached to polystyrene coated with poly-L-lysine were tested for their ability to bind specifically antigen-reactive cells in normal or primed mouse spleen. 88 to greater than 98% of the activity of cytotoxic populations was removed by a single adsorption. However, normal spleen cells or spleen cells previously primed in vitro could not be depleted of their capacity to be sensitized, even when adsorption effectively removed all residual cytotoxic activity from the same previously primed population. In fact, exposure to an immunoadsorbent augmented the ultimate cytotoxicity generated in a nonspecific fashion. This augmentation was especially dramatic in the case of a previously primed population and may have reflected the removal of a nonspecific suppressor. If antigen-reactive precursors cannot be removed efficiently by adsorption, other approaches to the generation of tolerant lymphoid populations, such as specific suppression of precursor differentiation must be sought.


1979 ◽  
Vol 149 (6) ◽  
pp. 1371-1378 ◽  
Author(s):  
B S Kim

Normal BALB/c spleen cells are unresponsive in vitro to the phosphorylcholine (PC) determinant in the presence of anti-idiotype antibodies specific for the TEPC-15 myeloma protein (T15) which carries an idiotypic determinant indistinguishable from that of most anti-PC antibodies in BALB/c mice. The possibility that idiotype-specific suppressor cells may be generated during the culture period was examined by coculturing the cells with untreated syngeneic spleen cells. Cells that had been preincubated with anti-T15 idiotype (anti-T15id) antibodies and a PC-containing antigen, R36a for 3 d, were capable of specifically suppressing the anti-PC response of fresh normal spleen cells, indicating that idiotype-specific suppressor cells were generated during the culture period. The presence of specific antigen also appeared to be necessary because anti-T15id antibodies and a control antigen, DNP-Lys-Ficoll, were not capable of generating such suppressor cells. Suppressor cells were induced only in the population of spleen cells nonadherent to nylon wool and the suppressive activity was abrogated by treatment with anti-Thy 1.2 serum and complement. These results indicate that anti-idiotype antibodies and specific antigen can generate idiotype-specific suppressor T cells in vitro. These in vitro results may reflect in vivo mechanisms of idiotype suppression.


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