scholarly journals Virus-replicating T cells in the immune response of mice. III. Role of vesicular stomatitis virus-replicating T cells in the antibody response.

1978 ◽  
Vol 148 (4) ◽  
pp. 850-861 ◽  
Author(s):  
N Minato ◽  
Y Katsura
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibody Response ◽  
Vesicular Stomatitis Virus ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Helper T Cell ◽  
Suppressor T Cell ◽  
Vesicular Stomatitis

The functional role of the T cell (Tv) which can replicate vesicular stomatitis virus (VSV) on activation by the antigen was investigated in antibody response in vitro. By the inoculation of VSV into the culture, marked augmentation of antibody response to sheep erythrocytes (SRBC) was observed in the culture of spleen cells taken more than 3 days after the immunization with SRBC, suggesting that the VSV-susceptible suppressor cells were included in these spleen cells and the activity was eliminated by the effect of VSV. Development of two distinct types of suppressor T cells was revealed in the spleen of mice after the priming with SRBC. First, nylon wool nonadherent (NAd) suppressor T cells found in the spleen cells taken 3 days after immunization, and second, nylon wool adherent (Ad) suppressor T cells found in the spleen cells taken approximately 1 wk after immunization. The activity of nylon Ad suppressor T cells was completely abolished by VSV-preinfection, whereas that of nylon NAd suppressor T cells was unaffected. It was also shown that the helper T-cell activity was not influenced by VSV-preinfection. These results provided direct evidence that nylon Ad suppressor T cell but not nylon NAd suppressor T cell nor helper T cell can actually replicate VSV after antigenic stimulation. Thus it was strongly suggested that Tv represents the nylon Ad suppressor T cells.

scholarly journals Virus-replicating T cells in the immune response of mice. II. Characterization of T cells capable of replicating vesicular stomatitis virus.

1978 ◽  
Vol 148 (4) ◽  
pp. 837-849 ◽  
Author(s):  
N Minato ◽  
Y Katsura
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Vesicular Stomatitis Virus ◽  
Major Part ◽  
Cell Activity ◽  
Helper T Cells ◽  
Suppressor T Cells ◽  
Helper T Cell ◽  
Vesicular Stomatitis

Immunocytological properties of the splenic T cell (Tv) which develop into virus plaque-forming cells in response to the antigenic challenge in vitro were investigated in relation to the properties of helper T cells and suppressor T cells in antibody response. Tv was observed in spleen around 1 wk after the intravenous injection of mice with 10(7) sheep erythrocytes. This contrasted with the finding that both helper T cells and suppressor T cells developed as early as 3 days after the immunization. Tv was proliferative in response to the antigenic stimulation, whereas helper T-cell activity could be expressed without cell division. Development of Tv to virus plaque-forming cells was much more dependent on macrophages than the generation of helper activity. Tv was found in nylon wool adherent fraction, whereas helper T cell was found in both nylon adherent and nonadherent fractions. Tv belongs to the short-lived and nonrecirculating T-cell population (T1), whereas the major part of helper T cells belongs to the long-lived and recirculating T-cell population (T2). These results strongly suggest that vesicular stomatitis virus infect and replicate in the different subset(s) of T cell(s) to which the major part of helper T cells belong.

scholarly journals Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. I. Detection and characterization of hapten-reactive suppressor T-cell activity in mice immunized with hapten-isologous protein conjugate

1977 ◽  
Vol 146 (1) ◽  
pp. 74-90 ◽  
Author(s):  
H Yamamoto ◽  
T Hamaoka ◽  
M Yoshizawa ◽  
M Kuroki ◽  
M Kitagawa
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Activity ◽  
Antibody Responses ◽  
Helper T Cells ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Helper T Cell ◽  
Suppressor T Cell

Helper and suppressor T-cell activities were detected simultaneously in the spleen cells of mice immunized with para-azobenzoate (PAB)-mouse gammaglobulin (MGG). Dinitrophenyl (DNP)-specific B cells were raised by immunization with DNP-keyhole limpet hemocyanin (KLH) and used as the indicator B-cell population. The helper and suppressor T-cell activities were determined after adoptively transferring spleen cells from PAB-MGG- primed donors and DNP-KLH-primed donors into X-irradiated recipients. Stimulation of these recipients with DNP-MGG-PAB detected helper T-cell activity, which was measured in terms of increased anti-DNP antibody responses of DNP-KLH-primed cells over these responses in the presence of unprimed cells. On the other hand, when DNP-KLH-primed cells were stimulated with DNP-KLH-PAB in the presence of PAB-MGG-primed cells, anti-DNP antibody responses were substantially lower than in unprimed normal cells. This suppressor cell population was (a) hapten-reactive, (b) present in B-cell-depleted spleen cells, (c) Thy-1 positive, (d) detectable earlier than the helper T-cell activities after priming (e) more radiosensitive than helper cells, and (f) found in the spleen but not the lymph nodes in contrast to helper T cells. These data indicate that these suppressor T cells are distinct from the helper T cells. PAB-reactive T cells clearly suppressed the antibody response by inhibiting KLH-reactive helper T-cell functions. The hapten-reactive T-lymphocyte system described here should be useful for analyzing and manipulating the immune response and for studying regulatory interactions of helper and suppressor T cells in the induction of antibody responses.

scholarly journals Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. II. Selective inactivation of hapten-reactive suppressor T cells by hapten-nonimmunogenic copolymers of D-amino acids, and its application to the study of suppressor T-cell effect on helper T-cell development

1977 ◽  
Vol 146 (1) ◽  
pp. 91-106 ◽  
Author(s):  
T Hamaoka ◽  
M Yoshizawa ◽  
H Yamamoto ◽  
M Kuroki ◽  
M Kitagawa
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Development ◽  
Cell Activity ◽  
Helper T Cells ◽  
Suppressor T Cells ◽  
Helper T Cell ◽  
Suppressor T Cell ◽  
Suppressor T Lymphocytes

An experimental condition was established in vivo for selectively eliminating hapten-reactive suppressor T-cell activity generated in mice primed with a para-azobenzoate (PAB)-mouse gamma globulin (MGG)-conjugate and treated with PAB-nonimmunogenic copolymer of D-amino acids (D- glutamic acid and D-lysine; D-GL). The elimination of suppressor T-cell activity with PAB-D-GL treatment from the mixed populations of hapten- reactive suppressor and helper T cells substantially increased apparent helper T-cell activity. Moreover, the inhibition of PAB-reactive suppressor T-cell generation by the pretreatment with PAB-D-GL before the PAB-MGG-priming increased the development of PAB-reactive helper T-cell activity. The analysis of hapten-specificity of helper T cells revealed that the reactivity of helper cells developed in the absence of suppressor T cells was more specific for primed PAB-determinants and their cross-reactivities to structurally related determinants such as meta-azobenzoate (MAB) significantly decreased, as compared with the helper T-cell population developed in the presence of suppressor T lymphocytes. In addition, those helper T cells generated in the absence of suppressor T cells were highly susceptible to tolerogenesis by PAB-D- GL. Similarly, the elimination of suppressor T lymphocytes also enhanced helper T-cell activity in a polyclonal fashion in the T-T cell interactions between benzylpenicilloyl (BPO)-reactive T cells and PAB- reactive T cells after immunization of mice with BPO-MGG-PAB. Thus inhibition of BPO-reactive suppressor T-cell development by the BPO-v-GL- pretreatment resulted in augmented generation of PAB-reactive helper T cells with higher susceptibility of tolerogenesis to PAB-D-GL. Thus, these results support the notion that suppressor T cells eventually suppress helper T-cell activity and indicate that the function of suppressor T cells related to helper T-cell development is to inhibit the increase in the specificity and apparent affinity of helper T cells in the primary immune response. The hapten-reactive suppressor and helper T lymphocytes are considered as a model system of T cells that regulate the immune response, and the potential applicability of this system to manipulating various T cell-mediated immune responses is discussed in this context.

scholarly journals Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amanda W. K. AuYeung ◽  
Robert C. Mould ◽  
Ashley A. Stegelmeier ◽  
Jacob P. van Vloten ◽  
Khalil Karimi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Vesicular Stomatitis Virus ◽  
Cell Response ◽  
Viral Infections ◽  
T Cell Response ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Cell Immunity ◽  
Vesicular Stomatitis

AbstractVaccination can prevent viral infections via virus-specific T cells, among other mechanisms. A goal of oncolytic virotherapy is replication of oncolytic viruses (OVs) in tumors, so pre-existing T cell immunity against an OV-encoded transgene would seem counterproductive. We developed a treatment for melanomas by pre-vaccinating against an oncolytic vesicular stomatitis virus (VSV)-encoded tumor antigen. Surprisingly, when the VSV-vectored booster vaccine was administered at the peak of the primary effector T cell response, oncolysis was not abrogated. We sought to determine how oncolysis was retained during a robust T cell response against the VSV-encoded transgene product. A murine melanoma model was used to identify two mechanisms that enable this phenomenon. First, tumor-infiltrating T cells had reduced cytopathic potential due to immunosuppression. Second, virus-induced lymphopenia acutely removed virus-specific T cells from tumors. These mechanisms provide a window of opportunity for replication of oncolytic VSV and rationale for a paradigm change in oncolytic virotherapy, whereby immune responses could be intentionally induced against a VSV-encoded melanoma-associated antigen to improve safety without abrogating oncolysis.

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 Identification of Igh-C-linked determinants on suppressor T cell hybrids and factors specific for L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT).

1985 ◽  
Vol 162 (3) ◽  
pp. 1044-1059 ◽  
Author(s):  
C M Sorensen ◽  
R J Hayashi ◽  
C W Pierce
Keyword(s):  
T Cells ◽  
T Cell ◽  
Polypeptide Chain ◽  
Spleen Cells ◽  
Suppressor T Cell ◽  
Cell Hybrids ◽  
Single Polypeptide Chain ◽  
Functional Classes ◽  
Single Polypeptide ◽  
Ig Allotype

Hyperimmunization of BALB/c mice with concanavalin A-stimulated blasts from the Ig allotype-congenic strain, C.B20, results in the production of antibodies reactive with T cells in an allotype-restricted manner. Spleen cells from these hyperimmune BALB/c mice were used to generate a panel of hybridomas that secrete monoclonal antibodies, reactive, in an allotype-restricted manner, exclusively with T cells subpopulations, and in particular, reactive with suppressor T cell hybridomas and their secreted soluble factors. Two functional classes of antibodies were identified: those that react with single polypeptide-chain suppressor T cell factors (TsF1) and the suppressor T cell hybridomas that produce such factors, and those that react with two polypeptide-chain suppressor T cell factors (TsF2) and their corresponding suppressor T cell hybridomas. These two classes of antibody were used to isolate molecules from the membranes of the respective suppressor T cell hybrids that are functionally and structurally related to the secreted suppressor T cell factors, suggesting a receptor function for these molecules.

scholarly journals Regression and inhibition of sarcoma growth by interference with a radiosensitive T-cell population.

1978 ◽  
Vol 148 (3) ◽  
pp. 799-804 ◽  
Author(s):  
K E Hellström ◽  
I Hellström ◽  
J A Kant ◽  
J D Tamerius
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Cell Population ◽  
Whole Body ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Irradiation Irradiation

BALB/c mice were inoculated subcutaneously with 10(6) cells from either of two syngeneic sarcomas 1315 and 1425. 6--8 days later, the mice were randomized into groups which were left untreated or given 400 rads of whole body irradiation. Irradiation significantly retarded the growth of both sarcomas, and complete regressions were seen of approximately equal to 30% of the small, established 1315 tumors. The anti-tumor effect of irradiation was abolished if the irradiated mice were inoculated with a T-cell-enriched (but not with a T-cell deprived) suspension of syngeneic spleen cells, suggesting that the irradiation inhibited tumor growth by affecting a radiosensitive population of host suppressor T cells.

scholarly journals Antigen- and receptor-driven regulatory mechanisms. IV. Idiotype-bearing I-J+ suppressor T cell factors induce second-order suppressor T cells which express anti-idiotypic receptors.

1980 ◽  
Vol 151 (5) ◽  
pp. 1183-1195 ◽  
Author(s):  
M S Sy ◽  
M H Dietz ◽  
R N Germain ◽  
B Benacerraf ◽  
M I Greene
Keyword(s):  
T Cells ◽  
T Cell ◽  
Specific Binding ◽  
Suppressor Cells ◽  
T Cell Subsets ◽  
Regulatory Pathway ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Suppressor Factor ◽  
Ig Heavy Chain

Administration of azobenzenearsonate (ABA)-coupled syngeneic spleen cells intravenously to A/J mice leads to the generation of suppressor T cells (Ts1) which exhibit specific binding to ABA-bovine serum albumin (BSA)-coated dishes. These Ts1 share idiotypic determinants with the major cross-reactive idiotype (CRI) of the anti-ABA antibodies of A/J mice, and also produce a soluble suppressor factor (TsF) bearing CRI and I-J subregion-coded determinants. Injection of this TsF into naive A/J mice elicits a second set of specific suppressor cells (Ts2) which are not lysed by anti-CRI antibody plus C, and which do not bind to ABA-BSA-coated dishes. However, in contrast with Ts1, these Ts2 do bind to plates bearing CRI+ anti-ABA immunoglobulin. Thus, Ts2 exhibit anti-idiotypic specificity. These data indicate that antigen elicits the production of a soluble T cell product bearing both variable portion of the Ig heavy chain (VH) and I-J subregion-coded determinants which serves to communicate between T cell subsets to establish an idiotype-anti-idiotype regulatory pathway.

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