scholarly journals Mechanism responsible for the induction of I-J restriction on TS3 suppressor cells.

1982 ◽  
Vol 156 (5) ◽  
pp. 1502-1515 ◽  
Author(s):  
M Minami ◽  
N Honji ◽  
M E Dorf

The mechanisms responsible for the induction of I-J restrictions on third-order suppressor T cells (TS3) were analyzed. The I-J phenotype of the antigen-coupled cells used for priming restricted the specificity of the TS3 population. Thus, TS3 cells were only generated after priming with antigen-coupled I-J homologous cells. Identity at the I-JM (and I-E) subregions was sufficient for TS3 induction. Furthermore, priming of H-2 heterozygous mice with antigen-coupled parental cells generated TS3 that were restricted to the parental haplotype used for priming. The splenic cell population responsible for antigen presentation and induction of TS3 cells was fractionated. The cells involved in antigen presentation were found in the splenic adherent population and were absent in the fraction containing splenic nonadherent T and B cells. The subsequent activation and interaction of TS3 cells is also restricted by genes in the H-2 complex. The results are discussed in terms of a general mechanism responsible for the induction of restrictions in T helper and TS3 cells.

1982 ◽  
Vol 156 (5) ◽  
pp. 1325-1334 ◽  
Author(s):  
M Takaoki ◽  
M S Sy ◽  
A Tominaga ◽  
A Lowy ◽  
M Tsurufuji ◽  
...  

The genetic restrictions of the activation of third-order suppressor cells (Ts3) were studied in mice, using two different types of anti-azobenzenearsonate (ABA)-immune responses, namely delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte (CTL) generation. Ts2 cells were induced in several different strains of mice by injecting monoclonal T hybridoma molecules or first-order suppressor factors (TsF1) originating in A/J (H-2a, Igh-1e) mice and then testing the TsF2 molecules derived from these Ts2 in A/J and A.By (H-2b, Igh-1e) or (A/J X A.By)F1 (H-2a/b, Igh-1e) and (C57Bl/6 X A/J)F1 (H-2b/a, Igh-1e) mice. It was shown that the activity of TsF2 was restricted to the I-J of the strain in which Ts2 was induced. By genetic analysis, restriction was shown to be due to the requirement of H-2 identity between ABA-coupled cells used for Ts3 activation and the strain of the TsF2 origin. Moreover, by using H-2-congenic ABA-coupled cells, we were also able to precisely map and demonstrate that ABA-coupled cells I-J identical to TsF2 induced in various strains were necessary for effective suppression to occur. This selective activation of Ts3 suggested the existence of I-J-related antigen presentation for suppression as the counterpart of I-A or I-A-I-E-restricted antigen presentation for positive immune responses.


1979 ◽  
Vol 150 (5) ◽  
pp. 1229-1240 ◽  
Author(s):  
M S Sy ◽  
B A Bach ◽  
A Brown ◽  
A Nisonoff ◽  
B Benacerraf ◽  
...  

Anti-p-azobenzenearsonate (ABA) antibodies, coupled covalently to normal syngeneic spleen cells and then given intravenously to normal animals, were found to be potent tolerogens for delayed-type hypersensitivity (DTH) to ABA. The ability of the antibody-coupled cells to induce tolerance was determined to be a result of the cross-reactive idiotype (CRI+) fraction of the antibodies, because anti-ABA antibodies lacking the CRI+ components when coupled to spleen cells were unable to cause any significant inhibition. Furthermore, genetic analysis revealed that the ability of CRI-coupled cells to inhibit ABA-specific DTH is linked to Igh-1 heavy chain allotype, in as much animals which possess heavy chain allotypes similar to that of A/J were sensitive to this inhibition. Adoptive transfer experiments provided evidence that CRI-coupled cells induce suppressor cells, and spleen cells or thymocytes from animals received CRI-coupled cells were able to transfer suppression to naive recipients. In addition, treatment with anti-Thy1.2 serum plus complement completely abrogated their ability to transfer suppression. Thus, this active suppression is a T-cell-dependent phenomenon. In investigating the specificity of these suppressor T cells, it was found that they functioned in an antigen-specific manner and were unable to suppress the development of DTH to an unrelated hapten 2,4-dinitro-1-fluorobenzene.


1979 ◽  
Vol 150 (5) ◽  
pp. 1216-1228 ◽  
Author(s):  
M S Sy ◽  
B A Bach ◽  
Y Dohi ◽  
A Nisonoff ◽  
B Benacerraf ◽  
...  

Delayed-type hypersensitivity (DTH) to the azobenzenearsonate (ABA) hapten can be readily induced in A/J mice injecting ABA-coupled syngeneic spleen cells subcutaneously. To further characterize this T-cell-dependent immunological phenomenon, the effect of passively administered anti-cross-reactive idiotype common to anti-ABA antibodies of A/J mice (CRI) antibodies on the development of ABA-specific DTH was investigated. Animals given daily injections (of minute amounts) of anti-CRI antibodies subsequent to immunization with ABA-coupled cells show significant reduction of ABA specific responses. This inhibition is antigen specific and requires the intact immunoglobulin molecule, as F(ab')2 treatments were ineffective in suppressing the reaction. Investigations of the mechanism of the anti-CRI-induced suppression of ABA DTH revealed that the observed suppression is a result of the activation of suppressor cells. Spleen cells taken from animals which received anti-CRI antibodies were able to adoptively transfer suppression to naive recipients. This suppression was shown to be mediated by T cells, as anti-Thy1.2 plus complement completely abrogated the transfer of suppression. In addition, animals pretreated with low doses of cyclophosphamide were not suppressed by the administration of anti-CRI antibodies. The genetic restriction of anti-CRI-induced suppression was demonstrated. Antibodies to the major cross-reactive idiotype, (CRI) associated with anti-ABA antibodies in A/J mice were unable to suppress the development of DTH to ABA in BALB/c mice (H-2d, Igh-1a). Such antibodies were, however, fully active in suppressing ABA DTH in the allotype-congenic C.AL-20 strain which has an allotype (Igh-1d) similar to that of A/J (Igh-1e) on a BALB/c background, and which produces humoral antibodies with the CRI.


1985 ◽  
Vol 162 (5) ◽  
pp. 1409-1420 ◽  
Author(s):  
I V Hutchinson ◽  
W H Barber ◽  
P J Morris

Suppressor T cells, activated by injection of trinitrobenzene sulphonic acid in DA rats, prevented rejection of LEW kidney allografts in a donor-specific manner when adoptively transferred into syngeneic recipients along with trinitrophenyl (TNP)-haptenated LEW alloantigen. TNP-haptenated third-party alloantigen was ineffective in this system. The donor-specific suppression was dependent, too, on the haptenic portion of the chemically modified alloantigen. Hence, fluorescein isothiocyanate-donor antigen did not lead to suppression in the presence of TNP-reactive suppressor cells. There is, however, some crossreaction between DNP- and TNP-haptenated alloantigens so that TNP-reactive cells and DNP-donor antigen suppressed rejection whereas DNP-reactive cells and TNP-donor antigen did not prevent graft rejection. The suppressor cells were sensitive to cyclophosphamide and radiation but were resistant to hydrocortisone. They appear to be T cells of the OX8 (suppressor/cytotoxic) phenotype since they are positive for the pan T cell antigen W3/13, are Ig negative, and do not carry the W3/25 (T helper cell) marker. However, these suppressor cells are adherent to nylon wool. They are found mainly in the spleen, are detected there within 2 d of TNBS injection, and can persist for up to 12 wk. We propose that these cells are first-order T suppressor (Ts1) cells that act in the afferent phase of the response to a renal allograft.


1981 ◽  
Vol 153 (6) ◽  
pp. 1533-1546 ◽  
Author(s):  
R K Gershon ◽  
D D Eardley ◽  
S Durum ◽  
D R Green ◽  
F W Shen ◽  
...  

We have described an interaction between two T cells subsets that results in interference with the expression of Ly-1-, 2+ (Ly-2) T cell-mediated suppression. We refer to this novel immunoregulatory activity as contrasuppression. The T cell responsible for the induction of contrasuppression (inducer cell) expresses the phenotype Ly-1-, 2+;I-J+;Qa-1+. This phenotype distinguishes it from the suppressor effector cells which we find to be I-J-2.3. An I-J+ soluble mediator from the contrasuppressor inducer cell acts on another cell (acceptor cell) that expresses the phenotype Ly-1+, 2+; I-J+; Qa-1+. This phenotype distinguishes it from T helper cells. Both the inducer cell (or its biologically active mediator) and its acceptor cell are required for the expression of contrasuppression. Because contrasuppressor cells can block the suppressive activity of cell-free mediators released by Ly-2 suppressor T cells, the mechanism of contrasuppression is either separated from or in addition to the inactivation of suppressor cells themselves. The potential importance of contrasuppressor activity in the regulation of suppressor T cell activity in allowing immunologic memory to be expressed and in permitting microenvironmental immune regulation is discussed.


1988 ◽  
Vol 36 (7) ◽  
pp. 711-715 ◽  
Author(s):  
L Kass

Using the polymethine dye p-ethoxyphenyl-p-aminostyryl-1,3,3-trimethyl-3H-indolium chloride as an aqueous stain applied to specimens of peripheral blood or buffy coat fixed in FAA fixative, differential coloration of leukocytes was achieved using darkfield illumination. Neutrophils stained dark maroon and contained green granules, eosinophils contained bright blue granules, basophils revealed yellow and pink granules, and monocytes stained green with green and yellow vacuoles. In studies of purified lymphocyte subpopulations obtained in a cell sorter, T-helper cells stained red, T-suppressor cells were yellow orange, B-cells appeared yellow and often contained yellow annular structures in the cytoplasm, and natural killer (NK) cells stained green and contained large green granules. As a rapid screening technique for identification of T-helper and T-suppressor cells and their ratios in health and disease, the new polymethine stain may complement the more complex monoclonal antibody techniques for identification of these cells.


1983 ◽  
Vol 158 (4) ◽  
pp. 1178-1190 ◽  
Author(s):  
Y Asano ◽  
R J Hodes

The present studies have identified cloned Lyt-1+2- T suppressor (Ts) cells that are both antigen specific and major histocompatibility complex (MHC) restricted in their activation requirements and that function to regulate the MHC-restricted activation of B cells by T helper (Th) cells. ParentA-restricted Ts clones suppressed, in antigen-specific fashion, the responses generated by (A X B)F1 Th cells cooperating with parentA (B plus accessory) cells, but did not suppress responses by the same (A X B)F1 Th cell population cooperating with parentB (B plus accessory) cells. Moreover, responses of (A X B)F1 leads to parentA Th cells and (A X B)F1 (B plus accessory) cells were suppressed by parentA-restricted Ts clones but not by parentB-restricted Ts clones. Thus, these findings suggest that the cloned Ts cells that have been characterized here function by specifically inhibiting the MHC-restricted interaction between Th cells and B and/or accessory cells. It was further demonstrated in experiments using cloned Th and Ts populations that these Lyt-1+2-Ts cells act not simply as inducers of suppressor but rather function in a restricted fashion as effector cells in the suppressor pathway.


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.


2001 ◽  
Vol 90 (5) ◽  
pp. 1736-1743 ◽  
Author(s):  
A. Choukèr ◽  
M. Thiel ◽  
V. Baranov ◽  
D. Meshkov ◽  
A. Kotov ◽  
...  

Because 6° head-down tilt (HDT) is an established method to mimic low gravity on earth, the aim of the present study was to determine the effects of 120-day HDT on psychic stress and peripheral blood immune cells in six healthy male volunteers. Psychological state was assessed by a current stress test, and cortisol was measured in saliva. During HDT, all volunteers developed psychic stress, and the diurnal rhythm of cortisol secretion was significantly altered. In addition, urine excretion of dopamine and norepinephrine increased. The innate part of the immune response was activated, as evidenced by the increase in the expression of β2-integrins on polymorphonuclear leukocytes and a rise in the number of circulating natural killer (NK) cell lymphocytes. The ratio of T-helper to T-cytotoxic and T-suppressor cells decreased, whereas no changes in T and B lymphocytes were observed. Plasma levels of interleukin-6 increased significantly and returned to basal levels after the end of the HDT period. Thus 6° HDT appears to be a valid model to induce psychic stress and neuroendocrine-related changes in the immune system, changes that might also be encountered by astronauts and cosmonauts during long-duration spaceflights.


1977 ◽  
Vol 146 (4) ◽  
pp. 970-985 ◽  
Author(s):  
C Waltenbaugh ◽  
J Thèze ◽  
J A Kapp ◽  
B Benacerraf

Injection of mice with L-glutamic acid50-L-tyrosine50 (GT)- or L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT)-specific suppressor T-cell factor (GT-TsF or GAT-TsF) up to 5 wk before antigenic challenge challenge suppresses GT-methylated bovine serum albumin (MBSA) and GAT-MBSA plaque-forming cells responses. T suppressor cells are responsible for the suppression induced by the suppressive extract as demonstrated by adoptive transfer and sensitivity to anti-Thy-1 and complement treatment. We conclude that suppressive extract induces specific suppressor T cells. The material responsible for generation of suppressor T cells is a product of the I subregion of the H-2 complex. We have excluded that suppressive quantities of antigens are present in the extract. A/J mice, which can neither be suppressed by GT nor make GT-TsF can be suppressed by BALB/c GT-tsf. Spleen cells from BALB/c GT TsF-primed A/J mice can adoptively transfer suppression to normal syngeneic recipients. A/J mice appear to be genetically defective in cells involved in factor production. These results are discussed in the light of a two-step model for induction of antigen-specific suppressor cells.


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