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Biomedical subjects

F Dumont

Publications and source records attributed to F Dumont.

At least 73 records · Page 4Linked to original sources
PubMed1982

Unusual cell surface properties of the T lymphocyte population expanding in MRL/Mp-lpr/lpr mice.

MRL/Mp-lpr/lpr (lpr/lpr) mice but not the congenic MRL/Mp-+/+ (+/+) mice, develop a generalized lymph node (LN) hypertrophy reflecting the expansion of a T-cell population that acts as an enhancing factor for autoimmunity. In order to characterize better this T-cell population, we investigated some of its surface properties in comparison with those of +/+ T cells. Electrophoretic measurements revealed that lpr/lpr T cells possess a lower electronegative surface charge than %/% T cells which indicates that the two cell types differ in the molecular composition of their plasmic membrane periphery. This notion was substantiated by the quantification of T- and B-cell markers and of lectin-binding sites on these cells using single- and two-colour flow cytofluorimetry. In agreement with recent observations by Lewis, Giorgi & Warner (1981) lpr/lpr T cells exhibited lower levels of Thy-1 and Lyt-1 antigens than +/+ T cells and were mostly devoid of Lyt-2 antigen. Although lpr/lpr lymph node (LN) cells displayed similar amounts of surface receptors for peanut agglutinin as +/+ LN cells, the expression of surface receptors for other lectins were either lower (Limulus polyphemus agglutinin, Maclura pomifera agglutinin, Concanavalin A) or higher (Helix pomatia agglutinin, Soya bean agglutinin, Bandeiraea simplicifolia agglutinin I, Phytohaemagglutinin L) on lpr/lpr T cells than on +/+ T cells. These data indicate that the T cells accumulating in hypertrophied lpr/lpr LN are endowed with unique surface characteristics which may explain some of the functional abnormalities of these cells.

Animals↗
PubMed1982

Lymphocyte subpopulations in the thymus of NZB x NZW mice: phenotypic characterization by flow cytofluorometry analysis.

The composition of the thymocyte population was investigated as a function of age in the autoimmunity-prone NZB x NZW F1 (NZB x W) female mice and in control BALB/c female mice. Single- and two-colour flow cytofluorometry analyses were used to quantitate the cell surface binding of fluorochrome-conjugated antibodies directed against various lymphocyte markers and of fluoresceinated peanut agglutinin (PNA). In both mouse strains, two major phenotypically distinct thymocyte subpopulations were thus identified. The predominant subpopulation was characterized as bright Thy-1+, Lyt-1 + 2+ and bright PNA+, and the other one as dull Thy-1+, Lyt-1 + 2- and dull PNA+. The relative frequencies of these two subpopulations were similar in NZB x W and BALB/c mice at 3 months of age. However, from 6 months onwards, slight but significant differences became detectable between the two strains. Thus, in BALB/c mice, both thymocyte subpopulations regressed at approximately the same rate during ageing so that their relative proportions remained constant. In contrast, in NZB x W mice, while the number of bright Thy-1+ cells diminished as in BALB/c mice, the number of dull Thy-1+ cells barely varied from 3 to 12 months of age, which resulted in a proportional increase of this latter subpopulation. Moreover, elevated frequencies of surface immunoglobulin-bearing cells were recorded in the thymus of 8-12 month old NZB x W mice but not in BALB/c mice. Therefore, the development of autoimmunity in NZB x W mice appears associated with an abnormal age-dependent evolution of the intrathymic lymphocyte population.

Aging↗
PubMed1982

Prepubertal orchidectomy induces thymic abnormalities in aging (NZB X SJL)F1 male mice.

Female but not male (NZB X SJL)F1 (NS) mice develop abnormalities of their intrathymic lymphocyte population in the course of aging. To determine the role played by androgens in this sex-related difference, we monitored the evolution of the cellular composition of the thymus in NS males deprived of androgens by prepubertal orchidectomy. Although in young mice this operation resulted in a twofold enlargement of the thymus, there was no histologic alteration or major change in the surface phenotype and mitogenic reactivities of the thymocytes, which suggests that all thymocyte subsets were increased to the same extent. In 12-mo-old control (BALB/c X SJL)F1 mice, prepubertal orchidectomy also produced an equal expansion (1.4-fold increase) of all thymocyte subsets. In contrast, in 12-mo-old orchidectomized NS males, there was a marked depletion of the thymic cortex and a hyperplasia of the medullary lymphoid tissue reflecting the selective expansion of a subset of phenotypically mature T cells (dull Thy-1+, Lyt-1+2+/-, dull PNA+) together with the emergence of intrathymic surface immunoglobulin-bearing cells. These latter cells probably represented B cells because there was a concomitant augmentation of the mitogenic responsiveness in vitro of thymic cell suspensions to lipopolysaccharide. Such thymic abnormalities induced by prepubertal orchidectomy in old NS males resemble those occurring spontaneously in the NS females. This suggests that the absence of thymic disease in intact NS males is primarily due to a suppressive effect of androgens.

Aging↗
PubMed1980

Lymphocyte subpopulations in the thymus of SJL/J mice: age-related alterations and the effect of spontaneous reticulum cell sarcoma development.

The cellular composition of the thymus was investigated as a function of age in the immunologically aberrant SJL/J mouse strain. Lymphocyte subpopulations were identified by combined analysis of cell electrophoretic mobility (EPM) and cell electronic volume and by assessment of surface receptor for Peanut-agglutinin (PNA) and of surface immunoglobulin (slg) determinants. In the thymus from young adult animals two major types of thymocytes could thus be recognized. The first one (th1, 2, 3) representing about 75% of the thymocyte population was endowed with a low-EPM and exhibited PNA-receptors. The other one (th4) possessed a high-EPM and lacked PNA-receptors. During ageing of mice selected for the absence of macroscopically detectable Reticulum Cell Sarcoma (RCS) lesions, the frequency of th1, 2, 3 cells diminished whereas that of th4 cells increased (up to 75% at the age of 16 months). This latter augmentation reflected a true expansion of the th4 cell subpopulation and acounted for the maintenance of thymus cellularity to a relatively high level throughout life. In accordance with the probable immunocompetence of th4 cells, thymus cell suspensions from old RCS-free SJL/J mice were found to exhibit high proliferative responses to T-cell mitogens. On the other hand, from the age of 8 months onwards, a new physical type of lymphocytes (th5) could be detected in increasing proportions. These cells were characterized by a lower EPM than typical th1, 2, 3 thymocytes and by a modal volume around 150 micrometer3. They were further demonstrated to be PNA- but slg+ and are thus likely to represent B cells. Such alterations were not encountered in BALB/c and DBA/2 mice in which both th1, 2, 3 and th4 thymocyte subpopulations regressed at approximately the same rate with age. Moreover, in the thymus of RCS-bearing SJL/J mice, the hyperplasia of the th4 cell pool and the occurrence of th5 cells appeared less important than in RCS-free mice.

Aging↗
PubMed1979

Peanut agglutinin (PNA)-binding properties of murine thymocyte subpopulation.

Surface receptors for peanut agglutinin (PNA), a lectin with D-galactose specificity, were detected on mouse thymocytes using fluorescence microscopy. Depending on mouse strain, 69-85% of unseparated thymocytes could thus be characterized as PNA+. Electrophoretic fractionation of thymocytes from normal or immunosuppressive drug-treated donors revealed an inverse relationship between PNA-binding properties and cell electrophoretic mobility (EPM). Thus, all thymocytes recovered in the lowest EPM fractions were strongly PNA+ whereas those in the highest EPM fractions were in the majority PNA-. Most of the cells collected in the intermediate EPM range were PNA+ but staining with the fluoresceinated lectin appeared weaker than for the low EPM thymocytes. Reciprocal experiments in which thymocytes were separated by PNA-mediated aggregation into fractions with different affinities for the lectin and then subjected to physical analysis, definitely established that PNA+ cells are of lower EPM than PNA- cells and that these two cell types also differ in size distribution. These data show that the four physical subpopulations of thymocytes previously described present distinctive PNA-binding properties: Th1 and Th2 cells can be classified as strongly PNA+, Th3 cells as less intensely PNA+, and Th4 cells as mostly PNA-.

Agglutination Tests↗
PubMed1979

T and B lymphocytes in pituitary dwarf Snell-Bagg mice.

The lymphocyte composition of the thymus and spleen from weaned (4 month old) hypopituitary dwarf Snell-Bagg mice were compared to those of their phenotypically normal littermates and of hormone (somatotropic hormone plus thyroxine)-treated individuals. Detection of cells bearing receptors for peanut agglutinin, physical analysis and measurement of in vitro reactivities to phytohaemagglutinin and concanavae intra-thymic lymphocyte population of dwarf mice. Examination of spleen-cell suspensions demonstrated a slightly higher frequency of T lymphocytes (Thy 1-2+ alpha-Naphthyl esterase+, high electrophoretic mobility) and lower frequency of B lymphocytes (surface immunoglobulin+, low electrophoretic mobility) in dwarf mice than in control mice. The degree of splenocyte responsiveness to T- and B-cell mitogens, however was similar in the two mouse types. High mobility (T) splenic cells were found to exhibit a smaller modal volume in dwarf mice (110 micron3) than in control mice (122 micron3) but this difference was not corrected by hormone administration. More pronounced were the quantitative differences between the spleens of hormone-deficient and normal mice. Thus, when expressed as a function of body weight, the numbers of splenic T and B lymphocytes in untreated dwarf mice were about half the corresponding values in hormone-reconstituted or normal littermates. These data suggested that in adult life, developmental hormones exert little direct effect on the thymus lymphocytes but influence the size of the pool of both peripheral T and B lymphocytes.

Animals↗
PubMed1978

Differential effect of hydrocortisone on lymphocyte populations in the mouse spleen.

The cellular composition of the spleen from CBA mice was investigated two days after administration of increasing doses of hydrocortisone acetate (HC), this using the presence of surface-immunoglobulin and the electrophoretic mobility as criteria for identification of lymphocyte populations. The B cell content was found to decrease more rapidly than did the T cell content. However, a significant diminution of the modal volume of both B and T cells was observed which suggests that HC acted similarly on each of these lymphocyte compartments by removing the larger elements. On the other hand, the in vitro reactivities to the B cell mitogens LPS and PPD were strongly depressed by HC injection while the reactivities to the T cell mitogens Con A and PHA remained relatively unchanged. Therefore, HC treatment appears to affect both B and T lymphocyte populations in the mouse spleen but the former to a greater extent than the latter.

Animals↗
PubMed1977

Electrokinetic properties and mitogen responsiveness of mouse splenic B and T lymphocytes following hydrocortisone treatment.

CBA mice recieved a single intraperitoneal injection of hydrocortisone acetate (OHC) in a dose of 125 mg/kg body weight. At various times therafter, electrophoretic mobility (EPM), surface immunoglobulin (SIG) and in vitro DNA synthetic reactivity to concanavalin A (ConA), phytohemagglutinin (PHA), lipopolysaccharide (LPS) and tuberculin (PPD) were investigated on splenic lymphocytes. OHC was found to deplete rapidly the spleen to a minimum of 18% of control cellularity by day 4 posttreatment. At this time, the proportions of low mobility (LM) and SIG-bearing lymphocytes (B cells) were reduced respectively to 28% (control 54%) and 20% (control 45%). The proportion of high mobility (HM) lymphocytes (T cells) was increased to 72% (control 45%). While the mean EPM of LM cells (0.71) was only slightly and transiently reduced, that of HM cells was significantly augmented (1.24) over control value (1.16). This latter finding was interpreted as indicating the selective removal by OHC of a T cell subpopulation with a mean EPM around 1.10. Changes in mitogenic responsiveness were consistent with these alterations of B and T cell compartments. Despite a marked drop in spontaneous 3H-thymidine uptake, the absolute response to T cell mitogens ConA and PHA remained relatively unchanged. By contrast, the reactivity to B cell mitogens LPS and PPD was strongly depressed. Starting by day 12, regeneration and normalizaiton of lymphocyte populations proceeded slowly and were not achieved before day 26-34.

Animals↗
PubMed1977

Changes in the electrophoretic mobility of mouse lymph node lymphocytes during ontogeny.

The electrokinetic properties of peripheral lymph node (LN) cells from C3H and nude mice aged 1, 3 or 10 weeks, were investigated by means of preparative and analytical cell electrophoresis. Two groups of cells were distinguishable throughout the age interval examined. The first group, with low-mobility (LM) included the majority of surface-immunoglobulin positive lymphocytes, was predominant in athymic nude mice and is thus likely to represent B cells. The other group, with higher mobility (HM), was sensitive to anti-Thy 1-2 serum, made up the major LN population in C3H mice and normal nude littermates and thus probably corresponds to T cells. In C3H mice, the relative proportion of LM cells was found to increase with age of LN donors (from 9-22%). Moreover, significant alterations in the mean electrophoretic mobility (EPM) of both lymphocyte populations were detected in the course of development. While the EPM of LM cells diminished from 0-81-0-70 micrometer.s-1.V-1.cm, that of HM cells increased from 1-11-1-22 micrometer.s-1.V-1.cm as the animals grew from 1-10 weeks. These observations indicate a relationship between the degree of maturity of peripheral B- and T-cell populations and their electrokinetic properties.

Animals↗
PubMed1976

Dose-related effect of hydrocortisone treatment on the electrokinetic properties and mitogen responsiveness of mouse thymocytes.

The electrophoretic mobility (EPM) and the ability to synthesize DNA in vitro either spontaneously or in response to concanavalin A (Con A) and phytohemagglutinin (PHA) were investigated on thymocytes from adult female Swiss/B mice which had received intraperitoneally, 2 days previously, various doses (10-750 mg/kg body weight) of hydrocortisone acetate (OHC). A first group of thymocytes, highly sensitive to OHC, rapidly decreased in proportion following administration of increasing doses of OHC (10-125 mg/kg body weight) and included the totality of low-EPM thymocytes (EPM less than 1.0 mum sec-1 V-1 cm) together with about 70% of the high-EPM thymocytes encountered in the normal thymus. The second group of thymocytes (4% of the initial cellularity), which resisted to OHC at 125 mg/kg body weight and was only reduced by half with doses of OHC 6-fold larger, was composed essentially of high-EPM cells. The mean EPM of both groups tended to increase with increasing doses of OHC which suggests that among these two groups thymocytes are all the more OHC-sensitive as they possess a low surface charge. Spontaneous DNA synthesis, measurable on the first 24 h of in vitro cultivation, markedly dropped after treatment with OHC at doses higher than or equal to 62 mg/kg body weight. This loss of early spontaneous proliferation coincided with the disappearance of medium-EPM thymocytes. By contrast, proliferative response of thymocytes to mitogens was enhanced by OHC pretreatment of donors and roughly paralleled the enrichment in high-EPM cells. However, administration of the largest amounts of OHC diminished this mitogen responsiveness, although PHA reactivity was less affected than Con A reactivity.

Animals↗