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J Martorell

Publications and source records attributed to J Martorell.

14 recordsLinked to original sources

IL-4 inhibits IL-2 synthesis and IL-2-induced up-regulation of IL-2R alpha but not IL-2R beta chain in CD4+ human T cells.

There is growing evidence to suggest a regulatory role of IL-4 in the immune system affecting both proliferation and lymphokine production. In the present work we have analyzed the effect of IL-4 on IL-2 and IFN-gamma synthesis by stimulating CD4+ human T cells (+10% accessory cells) with Con A in the presence of several doses (1 to 100 U/ml) of human rIL-4. The results showed an impaired IL-2 and IFN-gamma synthesis in the presence of IL-4. This inhibition was dose dependent and was evident only when IL-4 was added in the first 2 h of culture. Moreover, the external addition of IL-2 did not revert the inhibitory effect of IL-4 on IL-2 and IFN-gamma synthesis induced by Con A. We have also analyzed the effect of IL-4 on the expression of both alpha- and beta-chains of the IL-2R. Although the expression of IL-2R alpha mRNA was not modified after 6 h in culture in the presence of IL-4, a decrease was observed at 24 and 48 h. The addition of rIL-2 showed that the inhibition in IL-2R alpha expression could be explained by an impairment in the up-regulatory signal transmitted through the IL-2R. In addition to this, IL-4 did not modify the IL-2R beta mRNA expression at 6 and 24 h although a decreased expression was observed at 48 h which could be explained by the defective IL-2 production. The differential effect of IL-4 on the up-regulatory effect of IL-2 in the expression of IL-2R alpha and IL-2R beta suggest the existence of different regulatory mechanisms acting on the expression of both chains.

CD4-Positive T-Lymphocytes

CD27 induction on thymocytes.

CD27 mAb recognize a disulfide-linked homodimer of 55 kDa present in the majority of T cells and in a minor subpopulation of thymocytes. Although an increase of CD27 expression has been described in activated T cells, this Ag is poorly expressed in long term growing T cells. It has been also reported that CD27- becomes CD27+ upon activation. In the aim to better know the relationship between CD27 expression and the activation and maturation processes, the induction of this Ag in thymocytes was analyzed. The results obtained in this work show that: 1) CD27 is expressed only in thymocytes with high CD3 Ag density. 2) Its expression can be induced in low density CD3 CD4+ CD8+ cells by Con A and in low CD3 Ag density by PMA+ionomycin. 3) PMA alone or in combination with rIL-2 induces CD25 and CD71 expression but not CD27. 4) Unlike CD27, the Ag CD45RA, CD26, and CD76, which are present only in a minor thymocyte subpopulation, are not induced in double positive thymocytes. Because it has been reported that cyclosporin A interferes with thymocytes maturation and blocks the transition from double to single positive cells, its effect was measured on CD27 induction. Cyclosporin A did not inhibit CD25 expression induced by both Con A and PMA+ionomycin, but under these conditions it inhibited the induction of CD27. In this paper we discuss whether CD27 could be implicated in T cell maturation.

Antibodies, Monoclonal

Differential effects of anti-CD45 monoclonal antibody on human B cell proliferation: a monoclonal antibody recognizing a neuraminidase-sensitive epitope of the T200 molecule enhances anti-immunoglobulin-induced proliferation.

We have generated seven monoclonal antibodies (mAb) that recognize the T200 molecule. These mAb have been classified by competitive binding assay in flow cytometry into three groups each reacting with a different epitope of the T200 molecule: (a) 136-4B5, that shows a sialic acid nature, (b) 135-4H9, 135-4C5, 144-2, 155-2 and (c) 72-5D3, 124-2H12b. A heterogeneous effect was observed when they were tested on an anti-immunoglobulin-induced B cell proliferation. Whereas 72-5D3 and 135-4H9 mAb inhibited the proliferative response of B cells, 136-4B5 mAb greatly enhanced it, both effects being dose dependent. We can conclude that anti-CD45 mAb have a different and contrary functional behavior on anti-Ig-induced B cell proliferation, depending on the epitope recognized. The basis for such a difference could reside in the glucidic nature of the epitope recognized by the 136-4B5 mAb.

Antibodies, Anti-Idiotypic

Inhibitory effect of IL-4 on the sepharose-CD3-induced proliferation of the CD4CD45RO human T cell subset.

CD45R monoclonal antibodies are able to distinguish two different subsets of the CD4 human T cells. This phenotypic split is accompanied by functional diversity. In this report we have analyzed the capabilities of CD45R subsets of CD4 human T cells to use interleukin 2 (IL-2) and IL-4 as growth factors. We have found that both cell subsets are able to proliferate after stimulation with Sepharose-CD3 in the presence of externally added IL-2 or IL-4. However, the response to IL-4 of CD4CD45RO cells was comparatively lower than the response of CD4CD45RA cells. Both cell subsets showed a good response to Sepharose-CD3 plus adherent cells (AC), but when IL-4 was present in the culture only the CD4CD45RA cells showed an enhancement in the Sepharose-CD3-induced proliferation, while proliferation of the CD4CD45RO T cell subset was inhibited. Similar effects were seen, however, in the response to CD4CD45RA or CD4CD45RO cells to Sepharose-CD3 plus IL-2. Although the precise mechanism of the inhibitory effect of IL-4 is not known, the results obtained suggest that IL-4 could interfere in some way with the signalling of IL-2 to the proliferation of the CD4CD45RO T cell subset.

Antigens, Differentiation

Further data against HLA sharing in couples with recurrent spontaneous abortion.

Class I human leucocyte antigens (HLA-A, -B) and class II (HLA-DR) antigens were determined in 57 couples with primary recurrent abortions of unknown origin and in 57 normal fertile couples. No difference between abortion and control fertile couples was observed regarding HLA sharing. Analysis of 10 series in the literature, including our own results, is against the concept that compatibility in determinants of the major histocompatibility complex has a major role in recurrent spontaneous abortion (RSA).

Abortion, Habitual

Equilibrium binding of daunomycin and adriamycin to calf thymus DNA. Temperature and ionic strength dependence of thermodynamic parameters.

Absorbance and fluorescence quenching monitoring of the binding of the anthracyclines adriamycin (ADM) and daunomycin (DNM) to calf thymus DNA, provides reproducible binding data only when moderate drug/DNA molar ratios are used in the assays. Under these conditions, the fraction of DNA-bound drug, in equilibrium with free anthracycline, which can be reliably detected, ranged from 40-60% to 80-95% of the total added drug, depending upon ionic strength and temperature. Use of the neighbour exclusion model adequately fits such data and predicts that (i) the affinity of ADM for binding to the DNA is always higher than that corresponding to DNM, under similar experimental conditions, (ii) the binding constant for both drugs exhibits a strong salt and temperature dependence, and (iii) the exclusion parameter, indicative of the size of the anthracycline binding sites on the DNA, equals 3.1 +/- 0.4 and 3.3 +/- 0.4 base pairs for ADM and DNM, respectively, and is independent of salt concentration. The salt and temperature dependence of the binding constant is used to estimate the thermodynamic parameters involved in the interaction of the drugs with the DNA. Binding of the drugs is an exothermic process and the binding free energy arises primarily from a large negative enthalpy which, as the entropy, strongly depends upon ionic strength, and is much larger than predicted by polyelectrolyte theory. The enthalpy and entropy changes observed, appear to compensate each other over the entire range of salt concentrations used, and may arise from a complex variety of contributions, including salt-induced changes in secondary structure of the DNA, as indicated by circular dichroism techniques.

Animals

A second signal for T cell mitogenesis provided by monoclonal antibodies CD45 (T200).

The induction of T cell mitogenesis through CD3 is a complex process that requires at least two signals. The first one can be provided by Sepharose-bound CD3. The second one is normally provided by monocytes. The signal provided by Sepharose-bound CD3 is unable by itself to induce mitogenesis in monocyte highly depleted cells (MHDC). We describe here that the monoclonal antibody (mAb) 72-5D3 belonging to CD45 (T200), which was not mitogenic by itself, could replace monocytes when MHDC were activated by Sepharose-bound CD3. That is to say, in the absence of monocytes, mAb 72-5D3 gave a second signal necessary for T cell proliferation. Using eleven anti-CD45 mAb from other investigators we show that this effect is not a peculiar characteristic of 72-5D3 mAb. The effect of the mAb 72-5D3 was only effective in CD4-positive cells and was not observed when MHDC were activated with either soluble CD3 or concanavalin A. As both phorbol myristate acetate and mAb 72-5D3 can replace monocytes, a comparative study of their effects was undertaken. Phorbol myristate acetate but not mAb 72-5D3 induced proliferation of MHDC when recombinant interleukin 2 (rIL2) was added. On the other hand mAb 72-5D3 induced IL2 production in MHDC activated by Sepharose-bound CD3 and increased the IL2 production in Sepharose-bound CD3-activated peripheral blood mononuclear cells. In conclusion, data presented in this report indicate that the T200 molecule could be involved in T cell proliferation by giving a signal that induces the production of IL2 and bypasses the necessity of monocytes.

Animals

Shared HLA antigens between parents and recurrent spontaneous abortion.

Ten couples with a history of at least three (mean 3.8) consecutive spontaneous abortions of unknown etiology and 57 normal fertile couples (means 2.6 children) were tested for HLA antigens. The frequencies of shared HLA-A, -B and -DR antigens among members of the couples were similar in both groups. Our results, as well as analysis of the data in the literature, contradict HLA antigens sharing between parents as a determinant of recurrent spontaneous abortion.

Abortion, Habitual