scholarly journals Continuously proliferating allospecific T cells. I. Specificity of cooperation with allogeneic B cells in the humoral antibody response to sheep erythrocytes.

1979 ◽  
Vol 149 (4) ◽  
pp. 808-814 ◽  
Author(s):  
J D Waterfield ◽  
G Dennert ◽  
S L Swain ◽  
R W Dutton
Keyword(s):  
T Cells ◽  
B Cells ◽  
Humoral Response ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Strain Specificity ◽  
Sheep Erythrocytes ◽  
Effect Factor ◽  
Helper Activity

Allospecific mouse T cells, positively selected in one-way mixed lymphocyte culture were maintained for 3 yr in tissue culture by sequential restimulation. Such proliferating T cells were tested for their ability to induce a positive allogeneic effect: activating B cells in an in vitro primary humoral response to sheep erythrocytes. It was found that such T lymphocytes could function as helper cells. Helper activity was shown to be specific in that the B cells activated had to share major histocompatibility complex (H-2) antigens with the strain used for selection of the cell line. Intra H-2 mapping showed that antigens coded in the IAk subregion played an important role in the induction of the positive allogeneic effect. Supernatant factors could substitute for the allogeneic T cells in activation of the in vitro humoral response. However, such supernates exhibited no strain specificity. Therefore, the specificity seen in the positive allogeneic effect is presumably a consequence of the alloantigenic recognition receptors intrinsic to the T cells, and not to any biologically restricting properties of the allogeneic effect factor itself.

scholarly journals Helper function of T cells depleted of alloantigen-reactive lymphocytes by filtration through irradiated F1 hybrid recipients. I. Failure to collaborate with allogeneic B cells in a secondary response to sheep erythrocytes measured in vivo.

1976 ◽  
Vol 144 (3) ◽  
pp. 617-626 ◽  
Author(s):  
J Sprent ◽  
H von Boehmer
Keyword(s):  
T Cells ◽  
B Cells ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Secondary Response ◽  
F1 Hybrid ◽  
Sheep Erythrocytes ◽  
Helper Function ◽  
Lymph Node Cells

Helper T cells were obtained by injecting heavily irradiated semiallogeneic mice with lymph node cells from H-2-incompatible parental strain mice primed with sheep erythrocytes (SRC) 2 mo before. Thoracic duct lymphocytes collected from the recipents 18-40 h later (nearly all of which were theta-positive and of donor origin) were totally and specifically unresponsive against host-type determinants in mixed-lymphocyte culture. The filtered cells were transferred to irradiated semiallogeneic mice together with SRC and anti-theta-serum-treated (B) cells from SRC-primed syngeneic, semiallogeneic, or allogeneic mice. When antibody-forming cells were measured in the spleen 5-9 days later, effective IgM and IgG collaborative responses were observed with both syngeneic and semiallogeneic B cells but not with allogeneic B cells. No evidence was found that the failure to obtain collaboration with the allogeneic B cells was due to inhibition of the B cells by the T cells or vice versa.

scholarly journals Sequential responses of mouse spleen T cells in mixed lymphocyte culture-induced cytolysis.

1975 ◽  
Vol 141 (2) ◽  
pp. 508-512 ◽  
Author(s):  
P Häyry ◽  
L C Andersson
Keyword(s):  
T Cells ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Mouse Spleen ◽  
Blast Transformation

T cells triggered to blast transformation and proliferation by histoincompatible cells have the capacity of reverting "back" to lymphocytes. These "secondary" lymphocytes and their progeny cells are able to respond repeatedly to the same allogeneic stimulus in vitro.

scholarly journals Haplotype-specific suppression of cytotoxic T cell induction by antigen inappropriately presented on T cells.

1983 ◽  
Vol 157 (1) ◽  
pp. 141-154 ◽  
Author(s):  
P J Fink ◽  
I L Weissman ◽  
M J Bevan
Keyword(s):  
T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Cytotoxic T Cell ◽  
Spleen Cells ◽  
Specific Suppression ◽  
Veto Cells

To detect a strong cytotoxic T lymphocyte (CTL) response to minor histocompatibility (H) antigens in a 5-d mixed lymphocyte culture, it is necessary to use a responder that has been primed in vivo with antigen-bearing cells. It has previously been shown that minor-H-specific CTL can be primed in vivo both directly by foreign spleen cells and by presentation of foreign minor H antigens on host antigen-presenting cells. This latter route is evident in the phenomenon of cross-priming, in which H-2 heterozygous (A x B)F1 mice injected 2 wk previously with minor H-different H-2A (A') spleen cells generate both H-2A- and H-2B-restricted minor-H-specific CTL. In a study of the kinetics of direct- vs. cross-priming to minors in F1 mice, we have found that minor H-different T cells actually suppress the induction of virgin CTL capable of recognizing them. CTL activity measured from F1 mice 3-6 d after injection with viable A' spleen cells is largely H-2B restricted. The H-2A-restricted response recovers such that roughly equal A- and B-restricted activity is detected in mice as early as 8-10 d postinjection. This temporary hyporeactivity does not result from generalized immunosuppression--it is specific for those CTL that recognize the foreign minor H antigen in the context of the H-2 antigens on the injected spleen cells. The injected spleen cells that mediate this suppression are radiosensitive T cells; Lyt-2+ T cells are highly efficient at suppressing the induction of CTL in vivo. No graft vs. host reaction by the injected T cells appears to be required, as suppression of direct primed CTL can be mediated by spleen cells that are wholly tolerant of both host H-2 and minor H antigens. Suppression cannot be demonstrated by in vitro mixing experiments. Several possible mechanisms for haplotype-specific suppression are discussed, including inactivation of responding CTL by veto cells and in vivo sequestration of responding CTL by the injected spleen cells.

scholarly journals Phenotype, Localization, and Mechanism of Suppression of CD4+CD25+ Human Thymocytes

2002 ◽  
Vol 196 (3) ◽  
pp. 379-387 ◽  
Author(s):  
Francesco Annunziato ◽  
Lorenzo Cosmi ◽  
Francesco Liotta ◽  
Elena Lazzeri ◽  
Roberto Manetti ◽  
...  
Keyword(s):  
T Cells ◽  
Transforming Growth Factor ◽  
Mixed Lymphocyte Culture ◽  
Interferon Γ ◽  
Lymphocyte Culture ◽  
Target Cells ◽  
Suppressive Activity ◽  
Α Chain ◽  
Tgf Β1

Phenotypic markers, localization, functional activities, and mechanisms of action in vitro of CD4+CD25+ T cells, purified from postnatal human thymuses, were investigated. These cells showed poor or no proliferation in mixed lymphocyte culture (MLC), and suppressed in a dose-dependent fashion the proliferative response to allogeneic stimulation of CD4+CD25− thymocytes. Virtually all CD4+CD25+ thymocytes constitutively expressed cytoplasmic T lymphocyte antigen (CTLA)-4, surface tumor necrosis factor type 2 receptor (TNFR2), and CCR8. They prevalently localized to perivascular areas of fibrous septa and responded to the chemoattractant activity of CCL1/I-309, which was found to be produced by either thymic medullary macrophages or fibrous septa epithelial cells. After polyclonal activation, CD4+CD25+ thymocytes did not produce the cytokines interleukin (IL)-2, IL-4, IL-5, IL-13, interferon γ, and only a very few produced IL-10, but all they expressed on their surface CTLA-4 and the majority of them also transforming growth factor (TGF)-β1. The suppressive activity of these cells was contact dependent and associated with the lack of IL-2 receptor (IL-2R) α-chain (CD25) expression in target cells. Such a suppressive activity was partially inhibited by either anti–CTLA-4 or anti–TGF-β1, and was completely blocked by a mixture of these monoclonal antibodies, which were also able to restore in target T cells the expression of IL-2R α-chain and, therefore, their responsiveness to IL-2. These data demonstrate that CD4+CD25+ human thymocytes represent a population of regulatory cells that migrate in response to the chemokine CCL1/I-309 and exert their suppressive function via the inhibition of IL-2R α-chain in target T cells, induced by the combined activity of CTLA-4 and membrane TGF-β1.

scholarly journals Effect of activated lymphocytes on the regulation of hematopoiesis: enhancement and suppression of in vitro BFU-E growth by T cells stimulated by autologous non-T cells

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 1143-1147 ◽  
Author(s):  
M Harada ◽  
S Nakao ◽  
K Kondo ◽  
K Odaka ◽  
M Ueda ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Colony Growth ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
T Cell Subsets ◽  
Activated T Cells ◽  
Peripheral Blood Mononuclear ◽  
Erythroid Progenitor

Abstract Autologous mixed lymphocyte culture (AMLR) is an immunologic response with memory and specificity and plays a role in immune regulation. Effects of T cells activated by AMLR were studied in the regulation of in vitro erythropoiesis. AMLR-activated T cells were cocultured with autologous non-T, nonphagocytic peripheral blood mononuclear cells for assaying erythroid progenitor cells (BFU-E). T cells activated for 3 days in AMLR showed significant enhancement of in vitro colony growth by BFU-E. In contrast, activated T cells from day 7 AMLR caused significant suppression of BFU-E growth. Both enhancing and suppressing activities of AMLR-activated T cells were mediated by an la-positive and radiosensitive population within the OKT4+ subset. These observations suggest that AMLR-activated T cells may play a role in the immune-mediated regulation of in vitro erythropoiesis. It is also suggested that heterogeneous T-cell subsets may exert regulatory functions in the regulation of in vitro hematopoiesis.

scholarly journals Evidence that Lyb-2 is critical to specific activation of B cells before they become responsive to T cell and other signals.

1982 ◽  
Vol 155 (5) ◽  
pp. 1309-1316 ◽  
Author(s):  
H Yakura ◽  
F W Shen ◽  
E Bourcet ◽  
E A Boyse
Keyword(s):  
B Cells ◽  
Sheep Erythrocyte ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Cell Surface Molecules ◽  
Subsequent Generation ◽  
Spleen Cells ◽  
Soluble Factors ◽  
Surface Molecules

The generation of plaque-forming cells (PFC) to T-dependent antigen, but not to T-independent antigen, is reduced in vitro by Lyb-2 antibody. Monoclonal Lyb-2 antibody, added to Mishell-Dutton cultures within the first 2 d, but not later, greatly reduces the generation of alpha-sheep erythrocyte (SRBC) PFC from T-depleted spleen cells whether help is provided in the form of intact T cells or as soluble factors contained in mixed lymphocyte culture (MLC) supernatants. Generation of alpha-SRBC PFC from purified B cells, assisted by soluble factors in MLC and macrophage (P388D.1 cell) supernatants, is similarly reduced by Lyb-2 antibody. The initial 2-d period, during which cultures are diminishingly sensitive to reduction of PFC generation by Lyb-2 antibody, is not affected by the time at which such soluble factors are added. Thus, Lyb-2 cell surface molecules evidently do not function as receptors for these differentiative signals. Reduction of PFC generation by Lyb-2 antibody is antigen dependent in the sense that reduction of the PFC response to one antigen (SRBC) does not affect subsequent generation of PFC to a second antigen (horse erythrocytes) from the same cell population. These findings accord with the view that the Lyb-2 molecule participates in a B cell differentiative phase, probably proliferative, which begins with binding of antigen and precedes the phase in which B cells become fully receptive to signals from T and other cells.

scholarly journals B-cell precursors specific to sheep erythrocytes. Estimation of frequency in a specific helper assay.

1978 ◽  
Vol 148 (6) ◽  
pp. 1612-1619 ◽  
Author(s):  
M H Schreier
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Helper T Cells ◽  
Sheep Erythrocytes ◽  
Limiting Dilution Analysis ◽  
B Cell Precursors ◽  
Limiting Dilution

A sensitive, specific, and reproducible in vitro helper assay is described which is suited to limiting dilution analysis of murine B cells. 1 in about 3,000 syngeneic splenic B cells can be induced to form plaque-forming cells (PFC) to sheep erythrocytes in this system. The induction of PFC is absolutely dependent on antigen and specific helper T cells.

scholarly journals Effect of activated lymphocytes on the regulation of hematopoiesis: enhancement and suppression of in vitro BFU-E growth by T cells stimulated by autologous non-T cells

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 1143-1147 ◽  
Author(s):  
M Harada ◽  
S Nakao ◽  
K Kondo ◽  
K Odaka ◽  
M Ueda ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Colony Growth ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
T Cell Subsets ◽  
Activated T Cells ◽  
Peripheral Blood Mononuclear ◽  
Erythroid Progenitor

Autologous mixed lymphocyte culture (AMLR) is an immunologic response with memory and specificity and plays a role in immune regulation. Effects of T cells activated by AMLR were studied in the regulation of in vitro erythropoiesis. AMLR-activated T cells were cocultured with autologous non-T, nonphagocytic peripheral blood mononuclear cells for assaying erythroid progenitor cells (BFU-E). T cells activated for 3 days in AMLR showed significant enhancement of in vitro colony growth by BFU-E. In contrast, activated T cells from day 7 AMLR caused significant suppression of BFU-E growth. Both enhancing and suppressing activities of AMLR-activated T cells were mediated by an la-positive and radiosensitive population within the OKT4+ subset. These observations suggest that AMLR-activated T cells may play a role in the immune-mediated regulation of in vitro erythropoiesis. It is also suggested that heterogeneous T-cell subsets may exert regulatory functions in the regulation of in vitro hematopoiesis.

scholarly journals In vitro analysis of allogeneic lymphocyte interaction. II. I-region control of the activity of a B-cell-derived H-2-restricted allogeneic effect factor and its receptor during B-cell activation.

1978 ◽  
Vol 147 (4) ◽  
pp. 1198-1212 ◽  
Author(s):  
T L Delovitch ◽  
J Biggin ◽  
F Y Fung
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Lymphocyte Culture ◽  
B Cell Activation ◽  
Igg Antibody ◽  
Region Gene ◽  
Effect Factor ◽  
Ia Antigens

A genetically restricted allogeneic effect factor (AEF) derived from a mixed lymphocyte culture reaction between Ia-negative activated responder cells and irradiated T-cell-depleted stimulator cells was characterized. Restricted AEF is a B-cell-derived soluble helper factor which consists in part of Ia antigens controlled by the I-A subregion of the stimulator haplotype; additional control by the I-B, I-E, and I-C subregions, although unlikely, could not be excluded. This factor helps B cells of only its own haplotype or of haplotypes which carry an I-A and/or I-B subregion identity. Unprimed as well as hapten-primed Ia-positive B cells express a receptor for restricted AEF. The results indicate that the B-cell receptor for AEF is determined by the I-A subregion. Both restricted AEF and its receptor may therefore be products of the same I-region gene(s). The data are compatible with the hypothesis that the AEF Ia antigens serve as a second signal required for B-cell activation to IgG antibody production.

scholarly journals Competition between concanavalin A-induced stimulatory and inhibitory effects in the in vitro immune response to antigen.

1975 ◽  
Vol 141 (2) ◽  
pp. 524-529 ◽  
Author(s):  
J Scavulli ◽  
R W Dutton
Keyword(s):  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
Concanavalin A ◽  
Humoral Response ◽  
Inhibitory Effects ◽  
Spleen Cells ◽  
Con A ◽  
In Vitro Immune Response

The humoral response of nude spleen cells (b cells) to sheep erythrocytes was measured in the presence of varying numbers of concanavalin A (ConA)-acvated stimulatory spleen T cells (helper) and Con A-activated inhibitory spleen T cells (suppressor) from BDF1 mice. It was found that suppressive effects could be reversed by the presence of additional numbers of stimulatory cells. These results seem incompatible with the hypothesis that suppression is mediated by supraoptimal numbers of stimulatory cells and provides additional evidence that separate populations of T cells mediate stimulation and suppression.

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