scholarly journals T lymphocyte-mediated suppression of myeloma function in vitro. IV. Generation of effector suppressor cells specific for myeloma idiotypes.

1982 ◽  
Vol 155 (4) ◽  
pp. 1216-1221 ◽  
Author(s):  
A K Abbas ◽  
M Takaoki ◽  
M I Greene
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Suppressor Cells ◽  
Target Population ◽  
Mechanisms Of Action ◽  
Suppressor T Cells ◽  
Soluble Extract

BALB/c mice immunized intravenously with syngeneic splenocytes, to which affinity-purified IgA produced by the MOPC 315 myeloma is covalently coupled, develop suppressor T cells (Ts1) that inhibit IgA secretion by MOPC 315 cells after 3-4 d of co-culture. Immunization with M315-coupled splenocytes subcutaneously, followed by administration of a soluble extract of Ts1 cells, leads to the generation of effector Ts that are also idiotype specific and inhibit myeloma function within 1 d. Moreover, effector Ts are Lyt-1-2+, whereas Ts1 are either Lyt-1+2+ or require Lyt-1+ and Lyt-2+ cells to mature into effector Ts in vitro. Such a protocol should be useful for analyzing the interactions that result in the maturation of Ts and in defining the mechanisms of action of Ts, whose effect can be measured on a homogeneous target population and that are specific for a well-characterized myeloma idiotype.

scholarly journals Regulation of in vitro cytotoxic T lymphocyte generation. I. Evidence that killer cell precursors differentiate to effector cells in two steps.

1982 ◽  
Vol 155 (3) ◽  
pp. 783-796 ◽  
Author(s):  
A Schwartz ◽  
S L Sutton ◽  
R K Gershon
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Killer Cell ◽  
Suppressor Cells ◽  
Target Cells ◽  
Suppressor T Cells ◽  
Effector Cells ◽  
Step Process

The differentiation of cytotoxic T lymphocyte precursor cells (CTL-P) into CTL effector cells is a two-step process. In the first step, naïve CTL-P (CTL-PN) become activated (CTL-PA) but do not yet have the capacity to kill target cells. CTL-PA can be distinguished from CTL-PN because the former are far less sensitive than the latter to the effects of in vitro-generated suppressor cells. Thus, the addition of suppressor T cells (Ts) to a fresh MLC can totally inhibit the production of CTL from CTL-PN, whereas the same Ts only minimally affect the generation of CTL from CTL-PA. It is not known whether these Ts act directly on CTL-PN or on a helper cell needed for activation to CTL-PA. The production of CTL-PA can take place in allogeneic mixed leukocyte cultures (MLC) treated with the drug pyrilamine, or when heat-inactivated stimulator cells are used. Each of these treatments inhibits the differentiation of CTL-PA to CTL. However, if pyrilamine is removed, a nonspecific MLC-derived signal can induce these CTL-PA to become CTL, even in the presence of significant numbers of Ts. This two step process of differentiation of CTL-P to CTL may be analogous to the way naïve B cells become antibody-producing cells.

scholarly journals Mechanisms of idiotype suppression. I. In vitro generation of idiotype-specific suppressor T cells by anti-idiotype antibodies and specific antigen.

1979 ◽  
Vol 149 (6) ◽  
pp. 1371-1378 ◽  
Author(s):  
B S Kim
Keyword(s):  
T Cells ◽  
Specific Antigen ◽  
Suppressor Cells ◽  
Culture Period ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Myeloma Protein ◽  
Specific Suppressor T Cells

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.

IN VITRO GENERATION OF HELPER T CELLS AND SUPPRESSOR T CELLS THAT REGULATE THE CYTOLYTIC T LYMPHOCYTE RESPONSE TO TRINITROPHENYL-MODIFIED SYNGENEIC CELLS

1982 ◽  
Vol 33 (4) ◽  
pp. 422-426 ◽  
Author(s):  
NORBERT GUALDE ◽  
OFRA WEINBERGER ◽  
SHELDON RATNOFSKY ◽  
BARUJ BENACERRAF ◽  
Steven J. Burakoff
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Helper T Cells ◽  
Suppressor T Cells ◽  
Lymphocyte Response ◽  
Cytolytic T Lymphocyte

scholarly journals Suppressor cells: dependence on assay conditions for functional activity.

1976 ◽  
Vol 143 (5) ◽  
pp. 1211-1219 ◽  
Author(s):  
D D Eardley ◽  
M O Staskawicz ◽  
R K Gershon
Keyword(s):  
T Cells ◽  
Antibody Response ◽  
Functional Activity ◽  
Blood Cells ◽  
Suppressor Cells ◽  
Target Population ◽  
Spleen Cells ◽  
Regulatory Effects ◽  
Assay Conditions

Spleen cells educated in vitro with sheep red blood cells (SRBC) suppressed the plaque-forming cell response of Mishell-Dutton assay cultures challenged with optimal doses of SRBC. Changing conditions in the assay cultures changed the effect educated cells had on the assay culture responses. For example, educated cells helped rather than suppressed assay cultures of suboptimal numbers of spleen cells. Similarly, augmentation resulted upon addition of educated cells to assay cultures challenged with suboptimal doses of SRBC. Such a reversal of regulatory effects was not observed when assay cultures were challenged with supraoptimal antigen doses. Educated cells helped assay cultures of B spleen cells, and the addition of normal T cells reinstated suppression. Furthermore, maintenance of assay cultures under stationary rather than the usual rocking conditions allowed educated cells to help rather than suppress the antibody response of assay cultures. These results show that when the response of the target population (assay cultures) is low, the regulator (educated) cells augment the response, and vice versa, supporting the hypothesis that the effect regulator cells produce depends on the activity of the cells they regulate.

scholarly journals Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. XII. Fine specificity of anti-idiotypic suppressor T cells (Ts2).

1981 ◽  
Vol 154 (5) ◽  
pp. 1382-1389 ◽  
Author(s):  
D H Sherr ◽  
S T Ju ◽  
M E Dorf
Keyword(s):  
T Cells ◽  
Suppressor Cells ◽  
Cell System ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Fine Specificity ◽  
Cell Responses ◽  
Effector Phase ◽  
Different Levels

The fine specificity of anti-idiotypic, effector-phase suppressor T cells (Ts2) induced by the intravenous injection of syngeneic spleen cells covalently coupled with the 4-hydroxy-3-nitrophenyl acetyl (NP) hapten was studied in an in vitro plaque-forming cell system. By comparing the ability of these suppressor cells to bind monoclonal anti-NP antibodies that express different levels of serologically detected NPb idiotypic determinants, it was shown that anti-idiotypic suppressor T cells do not recognize the predominant NPb idiotypic determinants that are defined by serologic analysis. The implications for the possible expression and/or recognition of different sets of idiotypic determinants on T and B cells are discussed.

scholarly journals Differential major histocompatibility complex-related activation of idiotypic suppressor T cells. Suppressor T cells cross-reactive to two distantly related lysozymes are not induced by one of them.

1980 ◽  
Vol 152 (3) ◽  
pp. 521-531 ◽  
Author(s):  
L Adorini ◽  
M A Harvey ◽  
D Rozycka-Jackson ◽  
A Miller ◽  
E E Sercarz
Keyword(s):  
T Cells ◽  
T Cell ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Cross Reactivity ◽  
Suppressor T Cells ◽  
Cell Repertoire ◽  
Helper Cells

B10 (H-2b) mice are genetic nonresponders to hen egg-white lysozyme (HEL) and the distantly related human lysozyme (HUL). However, anti-HEL or anti-HUL primary antibody responses in vivo or in vitro can be obtained in B10 mice by immunization with the appropriate lysozyme coupled to erythrocytes. T cells able to suppress either anti-lysozyme plaque-forming cells (PFC) response are induced in B10 mice after immunization with HEL-complete Freund's adjuvant (CFA) or HUL-CFA. This cross-reactivity of HEL and HUL in the induction and the expression of suppressive activity is in marked contrast to their very low cross-reactivity at the PFC level. These results suggest that either HEL or HUL can stimulate a suppressor T cell which recognizes a particular epitope present on both lysozymes. Suppressor cells induced by HEL or HUL bear the same predominant idiotype found on the majority of anti-HEL antibodies, and on the small proportion of anti-HUL antibodies cross-reactive with HEL. B10.Q (H-2q) mice are responders in vivo to HEL-CFA, but not to HUL-CFA. In contrast to B10, HEL-CFA priming in B10.Q micr induces helper cells whereas HUL-CFA priming induces suppressor cells. These suppressor cells are cross-reactive with HEL and are fully able to suppress HEL-specific helper cells. The presence of HEL-specific suppressor cell precursors in B10.Q mice which are not activated by HEL, seems to implicate differential choice by the antigen presenting system as a basis for Ir gene control, rather than the absence of a regulatory cell type from the T cell repertoire.

scholarly journals Antigen mediation of a late-acting suppressor T-cell activity.

1977 ◽  
Vol 146 (6) ◽  
pp. 1627-1639 ◽  
Author(s):  
R W Warren ◽  
J M Davie
Keyword(s):  
Cell Activity ◽  
Suppressor Cells ◽  
Target Population ◽  
Target Cells ◽  
High Avidity ◽  
Suppressor T Cells ◽  
Specific Suppressor T Cells ◽  
Antibody Secretion ◽  
Antibody Secreting Cells

Carrier-specific suppressor T cells can suppress antibody secretion by high avidity IgG plaque-forming cells (PFC) within 90 min in vitro. This process can be blocked by the inclusion of soluble carrier in the cell mixture or by the exposure of target cells to anti-carrier antibodies or pronase. Moreover, suppression can be augmented by PFC exposure to the soluble hapten-carrier conjugate. Finally, carrier specificity may be overcome by preincubation of the target population with a hapten-heterologous carrier before addition of heterologous carrier ATC. Thus, it is likely that high avidity suppression depends upon immunogen bound to the surfaces of antibody-secreting cells which serves as a target for suppressor cells or molecules.

scholarly journals In vitro studies of the rabbit immune system. V. Suppressor T cells activated by concanavalin A block the proliferation, not the induction of antierythrocyte plaque-forming cells.

1976 ◽  
Vol 143 (4) ◽  
pp. 919-936 ◽  
Author(s):  
D Redelman ◽  
C B Scott ◽  
H W Sheppard ◽  
S Sell
Keyword(s):  
T Cells ◽  
B Cells ◽  
Concanavalin A ◽  
Peripheral Blood ◽  
Suppressor Cells ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Con A ◽  
Activated T Cells

The late B-cell proliferative phase of the in vitro antibody response by rabbit spleen cells is highly susceptible to suppression by activated T cells. The in vitro antisheep erythrocyte plaque-forming cell (PFC) response by spleen cells from normal or primed rabbits can be suppressed by adding concanavalin A (Con A), Con A-prestimulated peripheral blood or spleen lymphocytes, or supernates from Con A-prestimulated peripheral blood lymphocytes. The suppression is not mediated by a direct interaction of Con A with responding cells as shown by the effectiveness of prestimulated cells. Primed spleen cultures remain sensitive to Con A suppression as late as 72 h after initiation, and the addition of Con A after 24-72 h rapidly stops the increase in the number of PFC. T cells are required for Con A addition to be effective but the suppression can be induced at a time when T-helper cells are no longer necessary. Further, the suppressive effect of Con A addition is abrogated by specific antisera to rabbit T cells. We propose that Con A activates suppressor T cells which then exert their effects on proliferating PFC or their immediate precursor B cells. The early inductive or recruitment phase of the response is probably not blocked by suppressor cells. Also, there is an apparent relationship between the number of proliferating B cells and the number of suppressor cells required. Finally, the difficulties in inducing a stimulatory effect by Con A and the prolonged period that Con A addition is suppressive suggests that the rabbit has relatively more and/or longer-lived suppressor cells than the mouse and may be a particularly useful species for studying suppressive phenomena and their mechanisms.

In vitro induction of human suppressor T cells by a chorionic gonadotropin preparation

1981 ◽  
Vol 3 (2) ◽  
pp. 75-84 ◽  
Author(s):  
T. Fuchs ◽  
L. Hammarström ◽  
C.I.E. Smith ◽  
J. Brundin
Keyword(s):  
T Cells ◽  
Chorionic Gonadotropin ◽  
Suppressor T Cells ◽  
In Vitro Induction

Stimulation of activated rat T cells in vitro by Listeria monocytogenes antigens

1980 ◽  
Vol 29 (3) ◽  
pp. 1102-1110
Author(s):  
M C Woan ◽  
U K Forsum ◽  
D D McGregor
Keyword(s):  
T Cells ◽  
Listeria Monocytogenes ◽  
Soluble Extract ◽  
In Vitro Proliferation ◽  
Surface Immunoglobulin ◽  
Peripheral T Cells ◽  
Proliferation Of Lymphocytes ◽  
Antigen Presenting ◽  
Stimulation Of

A soluble extract of Listeria monocytogenes bound firmly and in similar amounts to a variety of rat cells. Cells that bound this material differed in their capacity to stimulate the in vitro proliferation of lymphocytes obtained from the thoracic duct of Listeria-immune donors. The capacity of cells to serve as antigen-presenting cells in this system coincided or closely overlapped the expression on these cells of an Ia antigen-like structure. Three lines of evidence indicate that T cells respond to L. monocytogenes antigen: the responder cells are members of a nylon-wool nonadherent population that lacks readily detectable surface immunoglobulin; they express determinants recognized by the W3/25 monoclonal antibody (a surface marker of rat peripheral T cells); and they are stimulated optimally by L. monocytogenes antigen when the latter is displayed on cells that share a haplotype with the responder lymphocytes.

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