scholarly journals Deficiency in suppressor T cell activity in aged animals. Reconstitution of this activity by interleukin 2.

1983 ◽  
Vol 157 (6) ◽  
pp. 2184-2189 ◽  
Author(s):  
M L Thoman ◽  
W O Weigle
Keyword(s):  
T Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Suppressor Cell ◽  
Spleen Cells ◽  
Suppressor T Cell

Spleen cells derived from aged (30 mo) C57Bl/6 mice are shown to be deficient in the ability to generate suppressor cell activity in vitro. The addition of IL-2 to cultures containing aged cells restores this function to a large extent.

scholarly journals Loss of suppressor T cells in adult NZB/NZW mice.

1976 ◽  
Vol 144 (3) ◽  
pp. 662-673 ◽  
Author(s):  
R S Krakauer ◽  
T A Waldmann ◽  
W Strober
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Activity ◽  
Suppressor Cell ◽  
Indicator System ◽  
Spleen Cells ◽  
Con A ◽  
Normal Cells ◽  
Suppressor T Cell ◽  
Cell Fractions

We have investigated suppressor T-cell activity in female NZB/NZW F1 mice using PWM-driven IgM biosynthesis in vitro as an indicator system. In initial we studied we observed that spleen cells from normal mice (BALB/c, C57BL/6), as well as from young (4 wk) and adult (18 wk) NZB/NZW mice, cultured in the presence of PWM synthesize 860 +/- 120 ng IgM/10(6) cells/7 days. However, when Con A (at 2 mug/ml) was added directly to the cultures (along with PWM), cells obtained from adult normal mice and young NZB/NZW mice showed a 94% suppression of IgM synthesis, whereas cells obtained from adult NZB/NZW mice were suppressed significantly less. To analyze these findings we studied the effect of Con A-induced suppressor cells (cells cultured with Con A for 24 h and washed free of Con A) on PWM-driven IgM biosynthesis. Spleen cells obtained from normal mice cultured in the presence of Con A-pulsed cells obtained from normal mice and young NZB/NZW mice showed an 83-88% suppression of PWM-driven IgM synthesis. Similarly, supernates obtained from Con A-pulsed cells of normal mice or of young NZB/NZW mice suppressed PWM-driven IgM synthesis. This suppression by Con A-pulsed cells and their supernates required T cells since T-cell fractions but not B-cell fractions eluted from anti-Fab Sephadex columns mediated suppression of co-cultured normal cells; in addition, Con A-pulsed cells treated with anti-theta and complement do not mediate suppression. These studies of Con A-induced suppressor cell activity in normal mice and young NZB/NZW mice contrast with studies of Con A-induced suppressor cell activity in adult NZB/NZW mice. We found that adult NZB/NZW Con A-pulsed cells and supernates obtained from the Con A-pulse cells had vastly decreased suppressor potential; in this case the Con A-pulse cells and supernatant fluids derived from such cells did not suppress PWM-driven IgM synthesis by normal cells. Finally, whereas spleen cells from young and adult NZB/NZW mice differ in their suppressor cell potential, cells from both sources could respond equally to suppressor signals in that Con A-pulsed normal cells or supernates derived from such cells caused equivalent suppression of PWM-driven IgM synthesis by young and adult NZB/NZW cells. These observations allow us to conclude that NZB/NZW mice lose suppressor T-cell activity as they age.

scholarly journals Antigen- and receptor-driven regulatorymechanisms. The failure of idiotype- coupled spleen cells to induce unresponsiveness in animals lacking the appropriate VH genes is caused by the lack of idiotype-matehed targets

1980 ◽  
Vol 152 (5) ◽  
pp. 1226-1235 ◽  
Author(s):  
M-S Sy ◽  
MH Dietz ◽  
A Nisonoff ◽  
RN Germain ◽  
B Benacerraf ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Spleen Cells ◽  
Suppressor T Cell ◽  
Recipient Animal ◽  
Vh Genes ◽  
In Vitro Treatment

A/J anti-p-azobenzenearsonate (ABA) antibodies bearing cross-reactive idiotypic (CRI) determinants, when coupled to spleen cells and then injected intravenously into naive animals, stimulate suppressor T cell (Ts) responses. Moreover, previous studies have demonstrated that the ability of such idiotype-coupled spleen cells to induce immune unresponsiveness to subsequent immunization with ABA-coupled spleen cells is linked to Igh-1 genes. Thus, CRI bearing antibodies from A/J mice, when conjugated to normal BALB/c spleen cells in vitro and then injected intravenously to syngeneic BALB/c mice, failed to induce tolerance in these animals. However, spleen cells taken from these animals transferred significant degrees of suppression to Igh-1 congenic C.AL-20 but not to H-2 congenic, Igh-1 distinct B10.D2 mice. Therefore, the failure of CRI-coupled spleen cells to induce suppressor cell- mediated unresponsiveness in animals unable to express the appropriate VH genes (i.e. BALB/c and B10.D2) appears to be caused by the lack of idiotype- matched targets. The notion that the ability to express certain Vn genes in the recipient animal is a prerequisite for suppressor cell function was further supported by the observation that suppressor cells induced in C.AL-20 mice failed to transfer any degree of suppression to BALB/c mice. The ability to transfer suppression from BALB/c mice to C.AL-20 mice is a T cell- dependent phenomenon, since in vitro treatment with anti-Thy 1.2 antiserum and complement completely abrogated suppressor cell function. Furthermore, these suppressor T cells are antigen specific and can be enriched on idiotype-coated petri dishes, indicating they possess anti-idiotypic receptors. Therefore, appropriate anti-idiotype and idiotype interaction is essential for the manifestation of suppressor T cell function in ABA-specific suppressor pathways.

scholarly journals CELL-MEDIATED IMMUNE RESPONSES IN VITRO

1974 ◽  
Vol 140 (2) ◽  
pp. 356-369 ◽  
Author(s):  
Duane L. Peavy ◽  
Carl W. Pierce
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cell Activity ◽  
Suppressor Cell ◽  
Regulatory Control ◽  
Cytotoxic Lymphocytes ◽  
Spleen Cells ◽  
Con A

The effects of soluble concanavalin A (Con A) or Con A-activated spleen cells on the generation of cytotoxic lymphocytes (CL) in mixed leukocyte cultures (MLC) were examined. Mitogenic concentrations of soluble Con A or small numbers of Con A-activated spleen cells substantially inhibited CL responses. The suppression was partial rather than absolute and was critically dependent upon the concentration and time of addition of soluble Con A or Con A-activated spleen cells to the MLC. Suppressive effects of Con-A activated spleen cells were mediated by T cells since suppressor cell activity was abrogated by treatment of spleen cells with anti-θ serum and complement before or after Con A activation. X irradiation of spleen cells before Con A treatment also abrogated generation of suppressor cell activity. After activation by Con A, however, the function of suppressor cells was radioresistant. Although the precise mechanism(s) of suppression is, as yet, unknown, the precursors of CL must be exposed to Con A-activated cells during the early phases of the immune response for suppression to occur. Kinetic studies revealed that suppression of CL responses was not due to a failure to initiate an immune response, but represented a response which developed initially, but subsequently aborted. The relevance of these observations to the concepts of T-cell-T-cell interaction and regulatory control of immune responses by T cells is discussed.

scholarly journals In vitro generation of antigen-specific helper T cells that collaborate with cytotoxic T-cell precursors.

1978 ◽  
Vol 148 (6) ◽  
pp. 1579-1591 ◽  
Author(s):  
L L Baum ◽  
L M Pilarski
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Cell Activity ◽  
Helper T Cells ◽  
Helper Cell ◽  
Cytotoxic T Cell ◽  
Spleen Cells

Antigen-specific helper T cells are required in the generation of cytotoxic T cells from thymocyte precursors. We have demonstrated that these alloantigen-specific helper cells can be generated in vitro and that both the quantity and quality of the helpers appear to be superior to the help obtained from unprimed spleen cells. Optimal helper cell activity is produced at day two of culture when CBA splenic helper precursors are stimulated by irradiated allogeneic spleen cells. Helper cell precursors are antigen-specific cells which cannot be instructed to express forbidden receptor specificities and bear theta antigen on their surface. The helper effectors are radioresistant, theta-bearing, and antigen-specific cells.

scholarly journals Antigen-specific suppressor T-cell activity in genetically restricted immune spleen cells.

1978 ◽  
Vol 148 (5) ◽  
pp. 1271-1281 ◽  
Author(s):  
C W Pierce ◽  
J A Kapp
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Activity ◽  
Antibody Responses ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Specific Suppressor T Cells ◽  
Immune Spleen Cells

Virgin spleen cells develop comparable primary antibody responses in vitro to syngeneic or allogeneic macrophages (Mphi) bearing the terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT), whereas immune spleen cells primed with syngeneic or allogeneic GAT-Mphi develop secondary responses preferentially when stimulated with GAT-Mphi syngeneic to the GAT-Mphi used for priming in vivo. These restrictions are mediated by products of the I-A subregion of the H-2 complex and are operative at the level of the GAT-Mphi-immune helper T-cell interactions. To investigate why these immune spleen cells fail to develop a significant antibody response to GAT-Mphi other than those used for in vivo immunization and determine the mechanism by which the restriction is maintained, spleen cells from virgin and syngeneic or allogeneic GAT-Mphi-primed mice were co-cultured in the presence of GAT-Mphi of various haplotypes. Antibody responses to GAT developed only in the presence of GAT-Mphi syngeneic to the Mphi used for in vivo priming; responses in cultures with GAT-Mphi allogeneic to the priming Mphi, whether these Mphi were syngeneic or allogeneic with respect to the responding spleen cells, were suppressed. The suppression was mediated by GAT-specific radiosensitive T cells. Thus, development of GAT-specific suppressor T cells appears to be a natural consequence of the immune response to GAT in responder as well as nonresponder mice. The implications of stimulation of genetically restricted immune helper T cells, and antigen-specific, but unrestricted, suppressor T cells after immunization with GAT-Mphi in vivo are discussed in the context of regulatory mechanisms in antibody responses.

On the role of monokines in the generation of nonspecific suppressor T cell activity in vitro

1994 ◽  
Vol 16 (2) ◽  
pp. 225-245 ◽  
Author(s):  
Constantin N. Baxevanis ◽  
George V.Z. Dedousis ◽  
Angelos D. Gritzapis ◽  
Nikolaos G. Papadopoulos ◽  
Paula Arsenis ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Activity ◽  
Suppressor T Cell

scholarly journals Generation of continuous large granular lymphocyte lines by interleukin 2 from the spleen cells of mice infected with Moloney leukemia virus. Involvement of interleukin 3.

1987 ◽  
Vol 166 (4) ◽  
pp. 833-849 ◽  
Author(s):  
M Hattori ◽  
T Sudo ◽  
M Iizuka ◽  
S Kobayashi ◽  
S Nishio ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Cdna Probe ◽  
Interleukin 2 ◽  
Cell Lineage ◽  
Constitutive Expression ◽  
Morphological Characteristics ◽  
Spleen Cells

Continuous cell lines could be reproducibly established by culturing spleen cells from adult mice injected with MLV-producer cells or directly infected with Mo-MLV with rIL-2, whereas the culture of normal splenic cells with rIL-2 induced only transient and limited proliferation resulting in no such lines. All of the lines showed morphological characteristics as LGL with Thy-1+,Lyt-1-,L3T4-,Lyt-2-,AsGM1+,FcR gamma+ phenotype without exception, and most of them exhibited typical NK-patterned cytotoxicity. Analysis of reverse transcriptase activity of the culture supernatants as well as Southern hybridization of the DNA from the lines using an Mo-MLV-specific cDNA probe indicated no evidence of retroviral replication or proviral integration, suggesting that the generation of cell lines reflected a reactive process and viral infection was not directly responsible. It was subsequently revealed that Thy-1+,Lyt-1+,Lyt-2- spleen cells from mice infected with Mo-MLV in vivo spontaneously produced surprising amounts of IL-3 in vitro, leading to the possibility that IL-3 was responsible for the generation of lines. The possibility was directly supported by the observation that continuous lines with identical characteristics could be generated completely in vitro by sequential stimulation with rIL-3 and rIL-2 from normal spleen cells without any involvement of Mo-MLV. The C beta gene of TCR was shown to be rearranged in all the lines examined, indicating the LGL lines were all genetically committed to T cell lineage. Unlike the situation in normal splenic populations expanded by rIL-2, where the expression of IL-2-R was progressively lost, constitutive expression of high-affinity-IL-2-R was observed in all the lines and thus, this was considered to explain the unlimited proliferation of them in response to rIL-2 alone. These results suggested the probable role of IL-3 in the regulation of growth and differentiation of a set of LGL committed to T cell lineage. The possible implications of the phenomenon in the regulation of hematopoiesis as well as in the control of Mo-MLV-induced leukemogenesis were discussed.

Sign in / Sign up

Export Citation Format

Share Document