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Biomedical subjects

M Debray-Sachs

Publications and source records attributed to M Debray-Sachs.

At least 37 records · Page 2Linked to original sources
PubMed1982

[Inhibition of insulin secretion of mouse pancreatic cells by T lymphocytes of insulin-dependent diabetics].

We previously showed that circulating lymphocytes from more than 90% of insulin-dependent diabetics, block extra insulin secretion induced by stimulatory media in mouse pancreatic cells in vitro, without altering the secretion of glucagon. The present work demonstrates that this phenomenon depends on lymphocytes having the OKT3 marker, i.e., thymodependent lymphocytes. However, OKT4+ T helper cells are not required for the above phenomenon as proved by experiments using monoclonal sera against the OKT4 marker. When diabetes is associated with other autoimmune diseases, the pancreatic lymphocyte cytotoxicity observed in vitro is inhibited by the addition of a normal lymphocyte population; this could indicate that a "suppressor" factor is lacking in these patients. Conversely, addition of normal lymphocytes does not prevent lymphocyte cytotoxicity in diabetics without associated autoimmune diseases. Such a difference confirms the present trend to make a distinction between these two categories of diabetes.

Adolescent↗
PubMed1982

In vitro inhibition of pancreatic B cell function by lymphocytes from diabetics with associated autoimmune diseases: a T cell phenomenon.

Lymphocytes from insulin-dependent diabetic patients were previously shown to suppress insulin release from mouse islet cells in vitro. Glucagon release was not suppressed. In order to further analyze this phenomenon, lymphocytes from three insulin-dependent diabetic patients with associated autoimmune diseases were treated by using the panning method for cell separation before testing on islet cell suspensions. The OKT3+, OKT3-, and OKT4- cell subsets were obtained. Insulin release was suppressed by the OKT3+ (T lymphocyte-enriched) subset, but not by the OKT3- (T lymphocyte-depleted) subset. These results suggest that T lymphocytes are directly involved in the suppression of insulin release in this model. Furthermore, the OKT4- (T helper-depleted) subset also suppressed insulin release.

Autoimmune Diseases↗
PubMed1981

[Inhibition of insulin secretion in vitro by serum of diabetic subjects in the presence of complement].

In order to explore complement-dependent humoral immunity in insulin-dependent diabetic patients, their serum was incubated with Mouse isolated pancreatic islets in the presence of complement, after which the response of these islets to glucose was estimated by measuring insulin secretion. Out of 13 sera from insulin-dependent diabetic patients, 5 caused a significant inhibition of the insulin response. Morphological observation of islets suggested that this inhibition was due to a cytotoxic effect of the sera. In the absence of complement, the same sera were not able to suppress insulin release. No beta-cell inhibition or morphological damage was detectable on islets incubated with sera from 13 healthy subjects and 4 non-insulin dependent diabetic patients, in the presence or in the absence of complement. Complement-dependent humoral immunity may play a role in the beta-cell injury of insulin-dependent diabetes.

Animals↗
PubMed1981

Lymphocytes from diabetics suppress insulin release in vitro.

The insulin response of isolated islet cells to glucose and theophylline in vitro was studied after incubation with lymphocytes. The test was employed to explore cell-mediated immunity in diabetics. A significant inhibition of insulin response to glucose and theophylline as compared to insulin release in a "basal" medium was found after incubation with blood lymphocytes from 21 out of 23 insulin-dependent diabetics (mean secretion index 18 +/- 18 versus 118 + 8 (SEM) % in control subjects). Most of the patients studied had associated autoimmune diseases: all of these displayed inhibition of insulin release. In six cases, the diabetes had a recent onset with no associated autoimmune disease: four of them displayed the same inhibition. No inhibition was found in the 26 control subjects and in seven non-insulin-dependent diabetics (mean secretion index 134 +/- 17 versus 145 +/- 23 (SEM) % in four control subjects). Lymphocytes inhibiting islet cell response were not cytotoxic against mouse fibroblasts. Twenty-two insulin-dependent diabetics showed islet cell antibodies to human and/or mouse pancreatic islets. However, an inhibition of insulin release was found with no detectable islet cell antibodies in one case, and the converse in two cases. Lymphocyte cytotoxicity to islet cells could play a role in the natural history of insulin-dependent diabetes.

Adolescent↗
PubMed1981

Complement-fixing Islet cell antibodies from some diabetic patients alter insulin release in vitro.

To explore humoral immunity in insulin-dependent diabetic (IDDM) patients, we studied insulin release from isolated mouse islets stimulated by glucose + theophylline after incubation with the sera of these patients and complement. Eleven of 21 IDDM sera suppressed the stimulated insulin release while the arginine-stimulated glucagon release remained unchanged. Morphologic evidence and the trypan-blue exclusion test suggested that the suppression of insulin release was due to a cytotoxic effect of the sera. No beta-cell inhibition of morphologic damage was detectable in the presence of sera from 30 healthy subjects, 8 non-insulin-dependent diabetic patients, and 5 nondiabetic patients with autoimmune diseases. Beta-cell inhibition by IDDM sera was not observed when complement was omitted. After serum fractionation, the cytotoxic potency of IDDM sera was located in the immunoglobulin G fraction. Using human islets, insulin release was suppressed by 3 of 6 IDDM sera. Complement-dependent cytotoxicity was found in 1 of 5 recent-onset IDDM patients and 11 of 16 IDDM patients with autoimmune phenomena. It was associated in all cases with the presence of islet cell antibodies as detected by immunofluorescence, and with the presence of circulating lymphocytes which suppressed insulin release in vitro. Complement-fixing antibodies may contribute to the selective beta-cell damage in IDDM.

Adolescent↗
PubMed1978

[Functional inhibition of isolated pancreatic cells, new technic for the detection of macrophage cytotoxicity].

It is usually accepted that macrophages "activated" by lymphokines may be found cytotoxic against tumoral target cells but show no detectable cytotoxicity in in vitro tests using normal non tumoral cells as target cells. These data have been obtained mainly with the chromium-release test. The present paper describes a new test using normal isolated pancreatic cells as target cells and evaluating the effect of activated or non-activated macrophages on the insulin secretion response to glucose stimulation. The results show a striking decrease in this response following an 18-hr incubation of pancreatic islet cells with activated macrophages, as compared to that of the same cells incubated with control macrophages. This is clear evidence that activated macrophages may alter normal cells and suggests that their cytotoxic properties are not restricted to tumoral target cells.

Animals↗
PubMed1978

[Cytotoxicity of mouse peritoneal cells after alloimmunization].

CBA Mice were immunized by two intraperitoneal injections of 30 X 10(6) DBA/2 or C57BL/6 spleen cells at days--12 and--2. Peritoneal cell population was obtained at day zero by washing the peritoneal cavity of Mice. Adherent cells were then separated using a 2 hrs. incubation in "Falcon" plates followed by washing. This macrophage-rich peritoneal cell population was found nonspecifically cytotoxic against 51Cr labeled tumoral target cells: P815 X DBA/2 mastocytoma cells, EL4 X C57BL/L lymphoma cells and spontaneous lymphoma AKR cells (same H--2k as CBA). This adherent peritoneal cell cytoxicity was demonstrated after 24 hrs. incubation with the target cells. It was found in nonspecific combination as well as when using target cells syngeneic to the donor. These findings suggest that adherent peritoneal cell cytotoxicity could be at least partly due to macrophages and result from factor (s) released by sensitized lymphocytes in vivo in the same way as has been previously demonstrated in vitro.

Animals↗
PubMed1978

Effect of thioglycollate on macrophage lysosomal enzymes.

Mice peritoneal macrophages obtained after i.p. injection of a medium containing thioglycollate (Institut Pasteur, Paris) have increased levels of beta glucuronidase and acid phosphatase, when compared with macrophages obtained without previous thioglycollate injection. The maximum increase is observed between 7 and 10 days after injection and reaches up to 3 to 4 times the normal activity. When using separately the various components of the medium, the same phenomenon may be observed but never to the same degree. The injection of thioglycollate also produces: a) an increase in total number of peritoneal cells, and b) an increase in the percentage of macrophages among these cells. Kinetic studies suggest that thioglycollate injection first induces an increase in the number of peritoneal macrophages and subsequently macrophage modifications resulting in lysosomal enzyme increase.

Acid Phosphatase↗