scholarly journals SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE

1973 ◽  
Vol 137 (2) ◽  
pp. 239-253 ◽  
Author(s):  
Robert E. Tigelaar ◽  
Richard Asofsky
Keyword(s):  
Normal Population ◽  
Lymphoid Cells ◽  
Spleen Weight ◽  
Spleen Cells ◽  
Parent Population ◽  
Graft Versus Host ◽  
Adult Mice ◽  
Peripheral Lymph ◽  
Normal Expression

Spleen cells from normal adult mice were injected into lethally irradiated adult syngeneic recipients. 24 h later, cell suspensions were prepared from the recipients' spleens or peripheral lymph nodes and tested either alone or combined for their capacity to elicit graft-versus-host (GVH) reactions in neonatal F1 recipients, using the Simonsen spleen weight assay. Either the lymph node-seeking subpopulation or the spleen-seeking subpopulation alone was markedly deficient in its ability to provide a GVH reaction when compared with the normal population from which it was derived. However, an appropriate mixture of the two had a reactivity characteristic of the parent population. Both subpopulations were sensitive to treatment with anti-θ antibody and complement in vitro. These results provide a convincing demonstration of the functional heterogeneity within the pool of thymus-derived cells present in a single normal lymphoid tissue. They strongly suggest that the normal expression of GVH reactivity of such a tissue involves an interaction among distinct subpopulations of thymus-derived cells.

scholarly journals IMMUNOCOMPETENCE OF SPLEEN CELLS FROM NEONATALLY THYMECTOMIZED MICE CONFERRED IN VITRO BY A SYNGENEIC THYMUS EXTRACT

1969 ◽  
Vol 130 (4) ◽  
pp. 765-775 ◽  
Author(s):  
Nathan Trainin ◽  
Myra Small ◽  
Amiela Globerson
Keyword(s):  
Host Response ◽  
Protein Concentration ◽  
Lymphoid Cells ◽  
Immune Reactivity ◽  
Spleen Cells ◽  
Graft Versus Host ◽  
Thymus Extract ◽  
Adult Mice ◽  
Thymectomized Mice

Impaired immunological competence of spleen cells from neonatally thymectomized C57B1/6 young adult mice was apparent when these cells were tested in an in vitro graft-versus-host assay. Spleen cell inocula prepared from thymectomized mice did not induce enlargement of (C3H/eb x C57BI/6)F1 newborn spleen explants, whereas the same number of cells from intact donors consistently initiated splenomegaly. Spleen enlargement was observed, however, when the explants were challenged by cells from thymectomized donors in the presence of syngeneic thymus extract, indicating that the spleen cells in suspension attained immunological competence under the influence of a non-cellular component of the thymus. Immunocompetence was also evident when the cells from thymectomized donors were first incubated with thymus extract for 1 hr and subsequently tested for reactivity. Cells from the same thymectomized donor mice exposed in parallel to extracts from syngeneic spleen or mesenteric lymph node at an equivalent protein concentration did not initiate a graft-versus-host response. These experiments demonstrate that immune reactivity in the graft-versus-host response involves activation of lymphoid cells by a humoral factor of the thymus acting directly upon these cells.

scholarly journals SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE

1970 ◽  
Vol 131 (2) ◽  
pp. 235-246 ◽  
Author(s):  
Harvey Cantor ◽  
Richard Asofsky
Keyword(s):  
Cell Types ◽  
Lymphoid Cells ◽  
Cell Populations ◽  
Lymphoid Tissues ◽  
Spleen Cells ◽  
F1 Hybrid ◽  
Graft Versus Host ◽  
Adult Mice ◽  
Thymus Cells ◽  
Old Mice

The capacity of cells from different lymphoid tissues obtained from Balb/c mice to produce graft-vs.-host (GVH) reactions was quantitatively determined in C57BL/6N by Balb/c F1 hybrid recipients. Synergistic responses were observed when small numbers of cells from lymphoid tissues that were rich in GVH activity such as spleen and femoral lymph node were combined with weakly reactive thymus cells. Thymus and spleen cells obtained from 1-wk old mice were separately inactive but produced moderate GVH reactions when combined in equal proportions. GVH activity of spleen cells from mice thymectomized at 3 days of age was partially restored by the addition of small numbers of spleen or thymus cells from adult mice. Changes in ratio between the two cell populations markedly affected the degree of synergy. Synergy was not observed when Balb/c cells were combined with Balb/c x C57BL/6N F1 hybrid cells and inoculated into C57BL/6N recipients, but was demonstrated when Balb/c and C57BL/6N cells were combined and inoculated into F1 recipients, indicating that a genetic disposition to mount GVH reactions in both populations is required to produce synergy. The data indicate that at least two cell types are necessary for GVH reactions, and that synergy between cell populations results from favorable adjustments in the ratio between these two cell types.

scholarly journals SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE

1970 ◽  
Vol 131 (2) ◽  
pp. 223-234 ◽  
Author(s):  
Harvey Cantor ◽  
Richard Asofsky ◽  
Norman Talal
Keyword(s):  
Host Response ◽  
Lymphoid Cells ◽  
Cell Populations ◽  
Spleen Cells ◽  
Graft Versus Host ◽  
Minimum Number ◽  
Number Of Cells

The ability of spleen cells from young (3 month) and old (1 yr) NZB mice to induce GVH reactions in newborn C57BL/6N mice was compared quantitatively using the Simonsen spleen assay. Young NZB cells were five times more reactive than cells from older mice. The minimum number of cells producing detectable reactions was 2 x 106 for the young and 10 x 106 for the old. Young and old cells combined and injected together produced GVH reactions quantitatively similar to those obtained with inocula composed of young cells alone. Mixtures of two cell populations producing no detectable reactions when injected separately into different recipients (1 x 106 young cells and 4 x 106 old cells) produced reactions approximately equal to those obtained with 5 x 106 young cells. As few as 0.25 x 106 young cells were sufficient to effect a reaction when combined with 4.75 x 106 old unreactive cells. Viability of both cell populations was essential for GVH reactivity. This evidence of synergy in GVH reactions indicates that old NZB spleen cells can be rendered immunologically more reactive in the presence of a normally reactive population.

scholarly journals HORMONE-LIKE ACTIVITY OF A THYMUS HUMORAL FACTOR ON THE INDUCTION OF IMMUNE COMPETENCE IN LYMPHOID CELLS

1974 ◽  
Vol 139 (1) ◽  
pp. 193-207 ◽  
Author(s):  
Abraham I. Kook ◽  
Nathan Trainin
Keyword(s):  
Adenyl Cyclase ◽  
Lymphoid Cells ◽  
Humoral Factor ◽  
Flufenamic Acid ◽  
Intracellular Camp ◽  
Immune Competence ◽  
Dibutyryl Camp ◽  
Spleen Cells ◽  
Antigenic Challenge

Experiments reported here were performed to understand the mechanism by which THF increases the immunocompetence of spleen cells from NTx mice. Dibutyryl cAMP or substances which increase intracellular levels of cAMP in lymphocytes such as Poly(A:U), theophylline, or PGE2 were shown to mimic the effect of THF and confer reactivity in an in vitro GvH response to spleen cells from NTx mice. Flufenamic acid, an antagonist to PGE2, was shown to inhibit the induction of competence by this substance. It was found that THF induces competence by activating membranal adenyl cyclase which leads to a rise in intracellular cAMP in thymus-derived cells only. These biochemical changes occur before antigenic stimulation and are unrelated to antigenic challenge. These findings indicate that THF exerts its effect via cAMP and are in agreement with the concepts which permit to classify THF as a thymus hormone.

scholarly journals Antilymphocytic antibodies and marrow transplantation. XII. Suppression of graft-versus-host disease by T-cell-modulating and depleting antimouse CD3 antibody is most effective when preinjected in the marrow recipient

Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2661-2667
Author(s):  
J Mysliwietz ◽  
S Thierfelder
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Ex Vivo ◽  
Experimental Studies ◽  
Prolonged Treatment ◽  
Antibody Activity ◽  
Spleen Cells ◽  
Host Disease ◽  
Graft Versus Host

Abstract A hamster antimouse CD3 monoclonal antibody (MoAb) opened the way to experimental studies on the suppression of allograft rejection and cytokine-related morbidity after treatment with antibodies modulating the CD3/T-cell receptor complex (CD3/TCR). Because earlier attempts to suppress graft-versus-host disease (GVHD) in patients by in vitro treatment of donor marrow with anti-CD3 MoAb had remained inconclusive, we used a rat IgG2b antimouse CD3 MoAb (17A2) with fewer side effects to analyze suppression of GVHD in the mouse model. Detailed phenotyping of blood, spleen, and lymphnode T cells after the injection of 400 micrograms 17A2 in C57BL/6 mice showed 60% CD3 downmodulation and 50% T- cell depletion for spleen cells. Injection of these spleen cells, together with bone marrow cells, in fully mismatched preirradiated CBA mice delayed GVHD by only 6 days. Ex vivo treatment of donor cells with 17A2 was not effective. In contrast, conditioning of marrow recipients with a single injection of 17A2 delayed 50% GVHD mortality by 100 days and prevented GVHD altogether after prolonged treatment, with survivors showing complete chimerism and specific transplantation tolerance. This difference in antibody effect contrasts with earlier experiences with nonmodulating but more strongly T-cell-depleting MoAbs of the same isotype, which prevent GVHD no matter whether applied in vitro or injected into donor or recipient mice. Our data indicate that CD3/TCR reexpression in marrow recipients with no circulating 17A2 is the reason why ex vivo donor cell treatment with anti-CD3 MoAb is comparatively ineffective. Our data, which allow separate evaluation of cell-depleting and cell-modulating antibody activity, help to explain previous clinical failure to suppress GVHD and provide evidence in favor of conditioning the marrow recipient with anti-CD3 MoAb as a therapeutic alternative.

scholarly journals Interaction of the v-Rel oncoprotein with NF-kappaB and IkappaB proteins: heterodimers of a transformation-defective v-Rel mutant and NF-2 are functional in vitro and in vivo.

1996 ◽  
Vol 16 (3) ◽  
pp. 1169-1178 ◽  
Author(s):  
D W White ◽  
G A Pitoc ◽  
T D Gilmore
Keyword(s):  
Dna Binding ◽  
Protein Interactions ◽  
Cellular Protein ◽  
Lymphoid Cells ◽  
Spleen Cells ◽  
Nf Kappa B ◽  
I Kappa B Alpha ◽  
Chicken Spleen

The v-Rel oncoprotein of the avian Rev-T retrovirus is a member of the Rel/NF-kappa B family of transcription factors. The mechanism by which v-Rel malignantly transforms chicken spleen cells is not precisely known. To gain a better understanding of functions needed for transformation by v-Rel, we have now characterized the activities of mutant v-Rel proteins that are defective for specific protein-protein interactions. Mutant v-delta NLS, which has a deletion of the primary v-Rel nuclear localizing sequence, does not interact efficiently with I kappa B-alpha but still transforms chicken spleen cells approximately as well as wild-type v-Rel, indicating that interaction with I kappa B-alpha is not essential for the v-Rel transforming function. A second v-Rel mutant, v-SPW, has been shown to be defective for the formation of homodimers, DNA binding, and transformation. However, we now find that v-SPW can form functional DNA-binding heterodimers in vitro and in vivo with the cellular protein NF-kappa B p-52. Most strikingly, coexpression of v-SPW and p52 from a retroviral vector can induce the malignant transformation of chicken spleen cells, whereas expression of either protein alone cannot. Our results are most consistent with a model wherein Rel homodimers or heterodimers must bind DNA and alter gene expression in order to transform lymphoid cells.

scholarly journals Dendritic cells induce antigen-specific regulatory T cells that prevent graft versus host disease and persist in mice

2011 ◽  
Vol 208 (12) ◽  
pp. 2489-2496 ◽  
Author(s):  
Uri Sela ◽  
Peter Olds ◽  
Andrew Park ◽  
Sarah J. Schlesinger ◽  
Ralph M. Steinman
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Graft Versus Host Disease ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Spleen Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
Naturally Occurring

Foxp3+ regulatory T cells (T reg cells) effectively suppress immunity, but it is not determined if antigen-induced T reg cells (iT reg cells) are able to persist under conditions of inflammation and to stably express the transcription factor Foxp3. We used spleen cells to stimulate the mixed leukocyte reaction (MLR) in the presence of transforming growth factor β (TGF-β) and retinoic acid. We found that the CD11chigh dendritic cell fraction was the most potent at inducing high numbers of alloreactive Foxp3+ cells. The induced CD4+CD25+Foxp3+ cells appeared after extensive proliferation. When purified from the MLR, iT reg cells suppressed both primary and secondary MLR in vitro in an antigen-specific manner. After transfer into allogeneic mice, iT reg cells persisted for 6 mo and prevented graft versus host disease (GVHD) caused by co-transferred CD45RBhi T cells. Similar findings were made when iT reg cells were transferred after onset of GVHD. The CNS2 intronic sequence of the Foxp3 gene in the persisting iT reg cells was as demethylated as the corresponding sequence of naturally occurring T reg cells. These results indicate that induced Foxp3+ T reg cells, after proliferating and differentiating into antigen-specific suppressive T cells, can persist for long periods while suppressing a powerful inflammatory disease.

scholarly journals Monoclonal antibodies reactive with the mouse interleukin 5 receptor.

1989 ◽  
Vol 169 (5) ◽  
pp. 1693-1701 ◽  
Author(s):  
A G Rolink ◽  
F Melchers ◽  
R Palacios
Keyword(s):  
B Lymphocytes ◽  
Cell Lines ◽  
Binding Sites ◽  
Lymphoid Cells ◽  
Sensitive Cell ◽  
Spleen Cells ◽  
Interleukin 5 ◽  
Cell Responses ◽  
Adult Mice ◽  
Proliferative Cell

The rat mAbs R52.120 and R52.625 inhibit the action of IL-5 on both IL-5-sensitive cell lines and freshly isolated splenic B lymphocytes. Neither antibody inhibits the proliferative cell responses promoted by IL-2, IL-3, or IL-4. Purified R52.120+ lymphoid spleen cells contain 15-20-fold higher numbers of B lymphocytes responding to IL-5 in the form of maturation into antibody-producing cells. By immunofluorescence staining and flow fluorocytometry, the R52.120 and R52.625 antibodies bound to all 12 IL-5-sensitive cell lines tested. Both antibodies react with 2-4% cells in the spleen, 5% lymphoid cells, and 10-15% myeloid cells in the bone marrow, and 10-14% in the peritoneum of C57BL/6, DBA/2, and BALB/c adult mice. No positive cells for either antibody were detected in the thymus and lymph nodes of these mice. Both R52.120 and R52.625 antibodies specifically inhibit the binding of radiolabeled IL-5 to its receptor. Finally, R52.120 and R52.625 antibodies precipitate from 35S-methionine-labeled IL-5-R+ cell lysates three proteins with Mr 46,000, 130,000, and 140,000. Taken together from these results, we conclude that the R52.120 and R52.625 mAbs recognize epitopes on the IL-5-R complex very close or identical to the IL-5 binding sites.

scholarly journals SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE

1972 ◽  
Vol 135 (5) ◽  
pp. 1059-1070 ◽  
Author(s):  
Robert E. Tigelaar ◽  
Richard Asofsky
Keyword(s):  
Lymph Node ◽  
Lymphoid Cells ◽  
Spleen Cells ◽  
Blood Leukocytes ◽  
Graft Versus Host ◽  
Average Survival ◽  
Lymph Node Cells ◽  
The One ◽  
Kinetics Of ◽  
Cell Inoculum

A mortality assay was used to quantitate graft-versus-host (GVH) reactions in sublethally irradiated (400 R) neonatal (C57BL/6 x BALB/c)F1 recipients of BALB/c lymphoid cells from various tissues. The probit of the 35 day cumulative per cent of mortality was a linear function of the logarithm of the cell inoculum for any tissue; reactivities of different tissues fell on a series of parallel lines. Peripheral blood leukocytes (PBL), the most active cells, were about 30 times as active as thymocytes, the least active cells studied; femoral lymph node cells and spleen cells were about 23 and 8 times as reactive as thymocytes, respectively. The average survival time of recipients of thymocytes who eventually died was nearly a week longer than that of recipients of comparably lethal numbers of PBL, lymph node, or spleen cells. Mixtures of PBL and thymocytes gave levels of 35 day mortality significantly greater than those expected if the reactivities of the mixture had been merely the sum of the reactivities of the components measured separately, thereby confirming in any assay independent of host splenomegaly the synergistic interaction of thymocytes and PBL in the GVH reaction. Both populations of cells in the mixture had to be allogeneic to the host in order to observe this synergy. The kinetics of cumulative mortality observed for mixtures of PBL and thymocytes were indistinguishable from those seen with thymocytes alone, indicating activation of the latter cell type. Finally, comparison of the relative abilities of different cell populations to cause splenomegaly on the one hand and lethal runting on the other has raised the possibility that expression of different effector functions of cell-mediated immune reactions may in fact be initiated by distinct cells.

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