Dissociation of interleukin-2 production from the cell activation in response to the mitogenic lectin in peripheral CD4+ T cells of LEC mutant rats (original) (raw)
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Immunology
Differentiation of naive T cells into effector cells producing T helper type 1 (Th1) and Th2 cytokines is regulated by the presence of specific cytokines in the T-cell microenvironment. The effect of interferon-γ (IFN-γ) and interleukin-4 (IL-4) on Th1- and Th2-like cell development was investigated in cultures of mixed rat spleen cells. These cells were cultured for 4 days in medium containing concanavalin A (Con A) with or without additional IL-2, IFN-γ or IL-4. The cells were then washed and their capacity to produce IL-4, IL-5 and IFN-γ determined following stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. Freshly isolated cells stimulated with PMA and ionomycin expressed detectable levels of IL-4 and IL-5 mRNA as measured by a quantitative polymerase chain reaction (PCR) procedure and much higher levels of IFN-γ mRNA. Cells cultured with Con A for 4 days, washed, and restimulated with PMA + ionomycin were unable to express detectable levels of IL-4 and IL-5 ...
Unresponsiveness of CD4-8+/- thymocytes to lectin stimulation in LEC mutant rats
Immunology, 1998
A mutant strain of rat, LEC, shows a novel arrest of T-cell maturation from CD4 + 8 + to CD4 + 8 but not to CD4-8+ cells in the thymus. The responsible mutant locus is designated the thid, which was acted upon in a recessive manner of inheritance. We found that LEC rat thymocytes failed to respond to interleukin (IL)-1, IL-6 and IL-7 in the presence of the mitogenic lectins, Allo A or concanavalin A (Con A). The unresponsiveness appeared to be due to unresponsiveness to the lectin stimulation rather than because of cytokine stimulation. Normal rat CD4-8+'-(consisting of CD4-8+ and CD4-8-thymocytes), CD4+'-8-(consisting of CD4+8-and CD4-8 -thymocytes), and CD4-8 -thymocyte subsets normally responded to mitogenic stimulation, while CD4+8+ thymocytes did not. In contrast, all LEC rat CD4-8+1-, CD4+'-8-,
The EMBO journal, 1989
The immediate upstream region of the mouse interleukin 2 (Il-2) gene harbors a strong transcriptional enhancer. This enhancer contains most, if not all of the sequence elements necessary for the T cell specific induction of the Il-2 gene by the phorbol ester TPA and the plant lectin Concanavalin A. DNase I footprinting studies with fractionated extracts obtained from induced and uninduced E14 T cells revealed numerous recognition sites for potential trans-acting factors. Five of these sites are also recognized by the TPA-activated HeLa cell factors AP-1 and AP-3. Other sites including two TATA-boxes, two purine-rich sequence motifs and two copies of the GGGPuTTTCAA motif are recognized by lymphocyte specific factors. The latter motif is highly conserved between several lymphokine genes and is therefore designated as a T cell element (TCE). In E14 T cells, pentamers of the distal TCEd confer an activity similar to that of the entire Il-2 enhancer, whereas in B and HeLa cells, the TCE...
Journal of Experimental Medicine, 1981
In the studies reported here, we have analyzed the production and consumption of T cell growth factor, more recently termed interleukin 2 (IL-2), as well as some cell-mediated immune functions, in murine strains [MRL, BXSB, NZB, and (NZB x NZWF1] manifesting systemic lupus erythematosus (SLE)-like syndromes. Young (4-6 wk) or old (4-8 mo) autoimmune or normal mice were studied and compared with regard to the following T cell functions in vitro after stimulation with concanavalin A (Con A): (a) mitogenic response; (b) IL-2 levels in culture supernates; and (c) the ability to respond to and adsorb IL-2. In addition, proliferative activity in the allogeneic mixed leukocyte culture and frequency of alloreactive cytotoxic T lymphocyte precursors (CTLp) were analyzed in some of these strains. Reduced Con A-induced mitogenic responses and IL-2 production appeared at 3-6 wk of age in the early, severe SLE developing strains MRL-Mp-lpr/lpr (MRL/l) and male BXSB and progressed thereafter. Sim...
The Journal of Immunology, 1996
T cells are considered to be of prime importance in immune regulation of both B and T cell functions. The targets of recognition in T-T cell interactions are not clear. Most recent experimental work has focused on the idiotypic regulatory interactions mediated by TCR peptides. There is experimental evidence that regulatory cells exist that do not recognize the TCR. This type of regulation is selectively induced by activated T cells. Therefore, we designed this study to examine the possible role of cytokine receptors as targets of immune regulation. We tested two peptides of IL-2R a-chain, 2 of IL-2R p-chain, and one of TNFR (p60). All peptides were found to be immunogenic at inducing T cell proliferation and four induced Abs in Lewis rats. We generated T cell lines to these five peptides, and tested them both in vitro and in vivo. We found that the T cells exhibited a proliferative response when cultured with activated, irradiated stimulator cells that were augmented upon addition of the cytokine receptor peptide. The cytokine profile of the lines was characterized as well as the Vp gene composition. One of the lines significantly protected against active encephalomyelitis. These results point at cytokine receptors as possible targets of immune regulation and T-T cell interactions.
Construction of Rat-Mouse T-Cell Hybridomas That Constitutively Produce Rat IL-2
Hybridoma, 1985
We have established rat-mouse T-cell hybridomas that constitutively produce rat Interleukin-2 (IL-2). T-cell hybridomas cannot be boosted to a higher level of IL-2 production by Con A stimulation. IL-2 prepared from T-cell hybridomas and from Con A activated rat spleen cells was partially purified using Ultrogel AcA 54 chromatography and ion exchange chromatography on Mono Q or chromatofocusing on Mono P. When analyzed on Mono P, IL-2 activity derived from IA2-B10 T-cell hybridoma eluted as a single peak with pH range 6.9-7.1, whereas IL-2 derived from Con A activated spleen cells resolved into four peaks within the following pH range: 7.1-7.2, 6.5-6.6, 6.1-6.2, and 5.6-5.7. Neuraminidase-treated IL-2 derived from Con A activated spleen cells resolved into single peaks appearing in the pH range 7.1-7.2. In contrast, neuraminidase treatment did not change the elution profile of IL-2 derived from the IA2-B10 hybridoma. IL-2 activity derived from the 3D6-B1 T-cell hybridoma also eluted as a single peak with the pH range 7.1-7.2. Neuraminidase treatment did not change the elution profile of IL-2. These data demonstrate that heterogeneity of IL-2 might be due to differences in the degree of glycosylation of IL-2 and differences in the sources of T-cells from which the IL-2 has derived. This work was supported by Grant-in-Aid from the Ministry of Education, Science, and Culture of Japan.
Journal of Clinical Investigation, 1995
Mercurials may induce immune manifestations in susceptible individuals. Mercuric chloride (HgCl2) induces autoimmunity in the Brown Norway (BN) strain but an immunosuppression in the Lewis strain with, however, autoreactive anti-class II T cells present in both strains. In the present study we looked at modifications of cytokine production by PCR and cytofluorometric analyses in normal BN and Lewis rat splenocytes, cultured with or without HgCl2. Unfractionated BN rat splenocytes and purified T cells exposed to HgCl2 expressed high levels of IL-4 mRNA. Increase in class II and CD23 molecule expression on B cells was partly inhibited by anti-IL-4 mAb showing that IL-4 was produced. By contrast, no overexpression of IL-4 mRNA could be seen in Lewis rats. Although an increase in class II molecule expression was observed suggesting that other T helper cell 2 cytokines were produced, there was also a concomitant decrease in CD23 molecule expression that was abrogated after addition of an anti-IFN-y mAb to the culture. IFN-y mRNA production was induced in unfractionated spleen cells and T cells from both strains after HgCl2 exposure. Altogether these findings demonstrate that HgCl2 has very early direct effects on cytokine production and that these effects differ depending on the strain. The early effect on IL-4 production observed on BN rat spleen cells and T cells may explain that the autoreactive anti-class II T cells that are found in HgCl2-injected BN rats have a Th2 phenotype. (J. Clin. Invest. 1995Invest. . 1484Invest. -1489.
Immunobiology, 1987
The ontogeny of the interleukin 2 receptor (IL 2 R) expression and of the IL 2 responsiveness has been investigated in the rat thymus. In tissue sections, IL 2 R-bearing cells were first detected at day 16 of gestation using the anti-IL 2 R mAb ART-18. In contrast to mice, IL 2 Rbearing cells of the rat are localized mainly in the thymic medulla from the first day of the corticomedullary compartimentalization, and not in the cortex. They are found in regions with a high expression of MHC class II antigens. The proportion of IL 2 R-bearing cells increases during gestation, reaches a peak at the first day after birth and declines to the adult level in the following weeks. The appearance of medullary localized IL 2 R-bearing cells is paralleled with the capacity of the thymocytes to proliferate in response to IL 2 without any additional stimuli.
International Immunology, 1998
We recently characterized a CD4 ⍣ T cell population expressing the IL-2Rα chain (CD25), producing IL-10 and resisting clonal deletion induced by viral superantigen (vSAG) encoded by mouse mammary tumor virus [MMTV(SW)]. We now report that these apoptosis-resistant cells are generated in the thymus but not from the immature CD4 ⍣ CD8 ⍣ thymocytes. They migrate from the thymus and are found in the periphery from at least the 10th day of life, after which they expand with the same kinetics in normal and MMTV(SW)-infected mice. Their strong capacity for expansion in the periphery makes this population insensitive to thymectomy in adulthood. CD4 ⍣ CD25 ⍣ cells were totally dependent on exogenous IL-2 for growth in vitro and in vivo, and were missing in IL-2 knockout (KO) mice. The absence of this population and/or an inability to produce IL-10 may be the missing link between IL-2Rα KO, IL-2 KO and IL-10 KO mice, which all die of inflammatory bowel disease.