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T H Ermak

Publications and source records attributed to T H Ermak.

At least 37 records · Page 2Linked to original sources
PubMed1989

Treatment of murine lupus with monoclonal antibody to L3T4. II. Effects on immunohistopathology of thymus, spleen, and lymph node.

Monoclonal antibody to L3T4 has been used successfully to suppress autoimmunity in the New Zealand black/New Zealand white F1 (B/W) mouse model for systemic lupus erythematosus. To clarify the immunopathology of murine lupus and determine the effects of anti-L3T4 treatment on the cellular composition and histopathology of lymphoid organs, we examined the distribution of lymphocyte subsets in cryostat sections of the thymus, spleen, and lymph nodes of B/W mice. Immunohistologic specimens were obtained from female B/W mice that had received weekly intraperitoneal injections of either rat monoclonal antibody to L3T4 (2 mg/mouse/week) or phosphate buffered saline (200 microliters/mouse/week) from age 5 months until euthanasia at 8 months. B and T cell domains in each organ were identified on serial sections with monoclonal antibody directed against B220 (all B cells), Thy-1.2 (all T cells), L3T4 (helper T cells), and Ly-2 (cytotoxic/suppressor T cells). In control mice, striking cytoarchitectural abnormalities were identified in the thymuses, and the spleen and lymph nodes were hypertrophied relative to anti-L3T4 treated mice. Thymic abnormalities included amplification of medulla, formation of thymomas, and cortical atrophy. Amplified medullary regions and thymomas in B/W mice contained numerous B cells and L3T4+ T cells but few Ly-2+ T cells. The enlarged spleens and lymph nodes of control mice consisted of numerous secondary follicles with germinal centers containing an unusual subpopulation of T cells that expressed L3T4 but not Thy-1.2. In contrast, mice treated with anti-L3T4 did not develop histopathologic changes characteristic of systemic lupus erythematosus in any organ. However, treatment depleted L3T4+ cells from the spleen and lymph nodes, and it modulated the expression of L3T4 by thymocytes. These observations demonstrate that treatment with anti-L3T4 not only interferes with L3T4-dependent T cell functions, but it also prevents progressive abnormalities in lymphoid tissue in lupus-prone B/W mice. This preservation of normal lymphoid structure may contribute to the beneficial effects of anti-L3T4 on autoimmunity.

Animals↗
PubMed1989

Uptake and translocation of fluorescent latex particles by rabbit Peyer's patch follicle epithelium: a quantitative model for M cell uptake.

A quantitative, light microscopic morphometric model for uptake of particulates by Peyer's patch M cells was developed. Rabbit intestinal loops containing Peyer's patches were inoculated with fluorescent, non-degradable polystyrene microparticles (600-750 nm), and their localization in Peyer's patches was traced after varying time periods. The particles were localized sequentially at the FAE cell surface, spanning the entire width of FAE cells, and within the subepithelial dome as a function of time. The particles were associated with 5D9+ or 1D9+ M cells, but were not taken up or transported by villus epithelia. The kinetics suggested a synchronous wave of uptake and transepithelial transport. Quantitative analysis revealed a considerably greater uptake efficiency of polystyrene microspheres in comparison to other biological particles.

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PubMed1989

M cells and granular mononuclear cells in Peyer's patch domes of mice depleted of their lymphocytes by total lymphoid irradiation.

The cytoarchitecture of Peyer's patches that were depleted of their lymphocytes by total lymphoid irradiation (TLI) was examined with particular attention to the effects on M cells in the follicle epithelium and on mononuclear cells in follicle domes underlying the epithelium. Five-month-old, specific pathogen-free Balb/c mice were irradiated with 200-250 rad/day, five times a week to a total dose of 3400-4250, and their Peyer's patches were either fixed for electron microscopy or frozen for immunohistochemistry 1-4 days after completion of irradiation. Control mice were examined at the same time intervals. Follicle domes of TLI mice had approximately one fourth the epithelial surface area of domes of control mice. Within the epithelium, lymphoid cells were virtually depleted after TLI, and yet the epithelium contained M cells. In control mice, most M cells were accompanied by lymphoid cells in invaginations of the apical-lateral cell membrane. In TLI mice, most M cells did not have such apical-lateral invaginations and were columnar shaped. Other than lacking lymphocytes, these cells appeared to be mature M cells. Some M cells did have lymphoid cells or granular mononuclear cells below their basal membranes, adjacent to the basal lamina. Below the epithelium, the proportion of granular mononuclear cells was greatly increased following TLI. The retention of M cells and the increase in proportion of granular mononuclear cells in follicle domes are consistent with selective depletion of lymphocytes following TLI. Persistence of M cells without lymphocytic invaginations after TLI suggests that M cells can differentiate in the absence of, or at least in the presence of very few, lymphocytes, and that invagination by lymphocytes is not necessary to maintain mature M cell morphology.

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PubMed1988

CD4-/CD8-T cells: amplification in spleens of mice following in vivo treatment with monoclonal antibody anti-L3T4.

Amplification of L3T4-/Ly-2-(CD 4-/CD 8-) T cells following in vivo administration of anti-L3T4 monoclonal antibody was examined in the spleen of mice by flow cytometry and immunohistochemistry. BALB/c mice were given 4-7 weekly injections of either anti-L3T4 (1 mg/week) or phosphate-buffered saline (control group), and dispersed spleen cells and tissue sections analyzed for the presence of Thy-1.2+, L3T4+, or Ly-2+ cells, and for the absence of both L3T4 and Ly-2 on Thy-1.2+ cells. Prior to treatment, L3T4+ and Ly-2+ cells accounted for virtually all Thy-1.2+ cells in approximately a 2:1 ratio. Following anti-L3T4 treatment, L3T4+ cells were depleted, and Ly-2+ cells accounted for about 2/3 of the Thy-1.2+ cells. A population of L3T4-/Ly-2- T cells was generated that accounted for 20-30% of the Thy-1.2+ cells, accounted for most of the Thy-1.2+ cells in red pulp, and was also present among the predominant Ly-2+ cells in periarteriolar sheaths.

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PubMed1988

Generation of L3T4-/Ly-2- T cells in Peyer's patches of mice treated with monoclonal antibody against helper T cells.

The effect of in vivo administration of anti-L3T4 monoclonal antibody on the generation of an L3T4-/Ly-2- (CD4-/CD8-) population of Thy-1.2+ cells was examined in Peyer's patches of mice by two-color flow cytometry. Female BALB/c mice aged 8 wk were given 4-6 weekly injections of either anti-L3T4 (1 mg/wk) or phosphate-buffered saline (control group), and dispersed Peyer's patch cells analyzed for the presence and absence of L3T4 and Ly-2 on Thy-1.2+ cells. In anti-L3T4 treated mice, L3T4-/Ly-2- T cells accounted for 25-30% of the Thy-1.2+ cells, whereas in control mice these cells represented only 3-4% of the T cells. The remaining 70-75% of the Thy-1.2+ cells after anti-L3T4 treatment were Ly-2+ and not L3T4+. The L3T4-/Ly-2- population of Thy-1.2+ cells is a novel subset which has not been previously found in Peyer's patches and is amplified when helper T cells are depleted.

Animals↗
PubMed1988

Treatment of murine lupus with monoclonal antibody to L3T4. I. Effects on the distribution and function of lymphocyte subsets and on the histopathology of autoimmune disease.

Monoclonal antibodies (MoAb) to L3T4 have been used successfully to suppress autoimmunity in murine models for several human autoimmune diseases. To clarify the immunologic and clinical consequences of treatment with anti-L3T4, we examined the effects of chronic administration of anti-L3T4 on the composition of lymphoid organs, the function of lymphocytes, and the histopathology of autoimmune disease in lupus-prone NZB/NZW F1 (B/W) mice. Weekly treatment with anti-L3T4 (2 mg/mouse) from age 5 to 8 months depleted L3T4+ cells from the spleen and lymph nodes, and prevented the development of splenomegaly and lymphadenopathy. The MoAb bound to target cells in the thymus and modulated their expression of the L3T4 antigen but, in contrast to its effect in extrathymic sites, anti-L3T4 did not deplete the target population from the thymus. In fact, after 3 months of therapy, mice that had been treated with anti-L3T4 had much larger thymuses than control mice that had been treated with saline, suggesting that treatment with anti-L3T4 prevented the thymic atrophy that occurs spontaneously in murine lupus. Despite depleting L3T4+ cells from the spleen, treatment with anti-L3T4 did not diminish the response of splenic lymphocytes to T and B cell mitogens, and it augmented splenic natural killer (NK) cell activity. Finally, treatment with anti-L3T4 decreased the diverse histopathologic manifestations of murine lupus. It dramatically reduced glomerular immunoglobulin and complement deposition and diminished lymphocytic infiltration and vasculitis in the kidneys. Treatment also reduced extrarenal immunopathology, including focal hepatitis and salivary gland infiltration. These observations have implications regarding the use of CD4 MoAb in people with autoimmune diseases.

Animals↗
PubMed1988

Modulation of lymphocyte subsets in Peyer's patches of mice treated with monoclonal antibody against helper T-cells.

Treatment of mice with anti-L3T4, a monoclonal antibody directed against helper T-cells, impairs clearance of intestinal Giardia muris infection. The present study examined the effect of anti-L3T4 treatment on mouse Peyer's patch cytoarchitecture and on the distribution of T-cell subsets within microenvironments of the follicle. Female BALB/c mice, aged 8 weeks, were given 4-7 weekly injections of either anti-L3T4 (1 mg/wk) or PBS (control group), and Peyer's patches were examined by immunohistochemistry or flow cytometry. In anti-L3T4-treated mice, Peyer's patch follicles (B-cell areas) were about two thirds the size of follicles in controls, and virtually all the size difference occurred in germinal centers. Peyer's patches were depleted of L3T4+ cells, yet the proportion of Thy-1.2+ (all T) cells was not decreased correspondingly, and the distribution of Thy-1.2+ cells in the patches was similar to that in control mice. In anti-L3T4-treated mice, Thy-1.2+ cells consisted of (a) Ly-2+ (cytotoxic/suppressor T) cells, and (b) a population of Thy-1.2+ cells that were neither L3T4+ nor Ly-2+. After treatment, Ly-2+ cells accounted for most of the T-cells in interfollicular areas and were also scattered in follicles, in germinal centers, and below the dome epithelium--in areas where L3T4+ cells predominated in control mice. Thy-1.2+ cells that were L3T4- and Ly-2- were mainly localized below the dome epithelium. These shifts indicate complex interrelationships among different lymphocyte subsets in Peyer's patches.

Animals↗
PubMed1988

Depletion and repopulation of lymphocytes in Peyer's patches of mice after total lymphoid irradiation.

The depletion and repopulation of lymphocytes in specific cellular domains of mouse Peyer's patches were examined following total lymphoid irradiation (TLI). BALB/c mice 5-months-old were given 17 fractionated doses of irradiation to a total of 3400 to 4250 rads over a 4-week period, and Peyer's patches were examined by immunohistochemistry at 1 to 4 days and 1 to 4 weeks after TLI. Cryostat sections were labeled with monoclonal antibodies directed against B220 (B cells), Thy-1.2 (all T cells), L3T4 (helper T cells), and Ly-2 (cytotoxic/suppressor T cells). In depleted mice, Peyer's patches were greatly reduced in size in comparison to controls, although the structural framework of follicles, domes, and interfollicular areas was still present. B cells in follicles were reduced to a small core of B220+ cells interspersed with nonlymphocytic cells. T cells were virtually eliminated from the patch except for a small population of Thy-1.2+ cells that were neither L3T4+ nor Ly-2+ in follicle domes. During early stages of repopulation at 1 to 2 weeks after TLI, follicles increased in size and were populated by helper T cells but Peyer's patches lacked discrete interfollicular T cell regions. At 3 to 4 weeks after TLI, T cell regions were found in interfollicular areas. The results indicate that morphologically distinct cellular domains are maintained in Peyer's patches after TLI which are sequentially repopulated by immigrating lymphocytes.

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PubMed1987

Clearance of Giardia muris infection requires helper/inducer T lymphocytes.

The aim of this work was to identify the T cell subset (helper/inducer or cytotoxic/suppressor) that plays a major part in the clearance of Giardia muris infection. BALB/c mice were selectively depleted of helper/inducer (Th/i) or cytotoxic/suppressor (Tc/s) T cells, by treatment with rat IgG monoclonal antibodies directed against the Th/i cell surface antigen L3T4, or against the Tc/s cell surface antigen Ly-2, and were infected with G. muris cysts. While mice depleted of Tc/s cells cleared G. muris infection at a normal rate, mice depleted of Th/i cells did not clear the infection. Depletion of the relevant T cell subset was confirmed by flow cytometry and by immunohistochemistry. The data indicate that helper/inducer T cells, but not cytotoxic T cells, are of major importance for elimination of G. muris from the mouse intestine.

Animals↗
PubMed1987

Phenotype and distribution of T lymphocytes in Peyer's patches of athymic mice.

The distribution and phenotype of T (Thy-1.2+) cells was examined in Peyer's patches of 8 and 16 week old athymic mice by peroxidase and two-color-fluorescence immunohistochemistry. Despite the generally recognized T cell deficiency of nude mice, some T cells consistently occurred in Peyer's patch domes in all mice. However, many Thy-1.2+ lymphocytes lacked cell surface markers for either helper T cells (L3T4) or cytotoxic/suppressor T cells (Lyt-2), indicating that these cells may be an immature subset of T cells. These cells may represent a population of resident T cell precursors delayed in maturation or T cells newly immigrated to Peyer's patches.

Animals↗
PubMed1986

Differential distribution of lymphocytes and accessory cells in mouse Peyer's patches.

The aim of this immunohistologic study was to determine how lymphocytes and accessory cells associated with antigen processing are distributed in the domes of Peyer's patches. Monoclonal antibodies against mouse B cells (anti-B220), T cells (anti-Thy-1.2), T helper cells (anti-L3T4), T cytotoxic/suppressor cells (anti-Lyt-2), macrophages (anti-Mac-1), and Ia+ cells (anti-I-Ad) were applied to cryostat sections of mouse Peyer's patches and visualized with peroxidase-conjugated avidin-biotin complexes (ABC). The subepithelial dome, the dome epithelium, and the follicle crypt epithelium were ech surveyed for cells labeled with these antibodies. Each region had a characteristic and nonrandom distribution of labeled cells. In the subepithelial dome, B cells, T helper cells, macrophages, and Ia+ accessory cells formed a cellular meshwork between follicle and the dome epithelium. T cytotoxic/suppressor cells were sparse beneath the epithelium. In the dome epithelium, solitary and paired lymphocytes occurred both above and below the level of epithelial cell nuclei. B cells predominated, and both T helper cells and T cytotoxic/suppressor cells were present. B cells sometimes aggregated in small clusters. Macrophages were rarely observed in the epithelium. The distribution of cells in the dome epithelium was distinctly different from non-Peyer's patch intestine where T cytotoxic/suppressor cells predominated and B cells were few in number. Although lymphocytes were usually absent in crypts outside Peyer's patches, in follicle crypts B cells and T cells were seen but not Ia+ accessory cells or macrophages. Most of the T cells in the crypt epithelium were T cytotoxic/suppressor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Zymogen granule size in pancreas of nursing rats.

Dramatic depression in granule volume density and size was measured in acinar cells of postnatal rat pancreas following the initiation of feeding. Volume density decreased about threefold from 45% at birth to 16% 2 days thereafter. Mean granule diameter decreased from 1.50 micron to 0.80 micron, an 85% decrease in corresponding granule volume. At the same time, numerical density approximately doubled. At 2 days after birth, cells with smaller granules had lower volume densities, and differences in mean granule volume between cells accounted for most of the differences in volume density. Although the distribution of granule diameter in newborns was lognormal, the distribution at 2 days was heavily skewed to larger sizes. This was the result of skewed distributions within individual cells and not an artifact of sampling. The results corroborate the central role of granule volume in determining changes in the volume density of zymogen granules in the pancreas and suggest that zymogen granules can act as capacitors that can change size as a function of the enzyme contained within.

Aging↗
PubMed1983

Increase in zymogen granule volume accounts for increase in volume density during prenatal development of pancreas.

The sudden increase in volume density of zymogen granules in acinar cells of the fetal rat pancreas was examined with particular attention to the respective roles of granule size and number in this event. Volume density increased some twelvefold, from about 3% of cytoplasmic volume at 17 days to about 45% at 20 days, following a sigmoidal pattern in which the greatest rate of increase occurred during day 18. This increase in volume density was primarily the result of an increase in granule volume. Zymogen granule diameter increased from 0.55 micron at 17 days to 1.20 micron at 20 days, an order of magnitude increase in average granule volume. The total number of granules in the tissue increased in proportion to the increase in organ weight (cell number and size), but changes in the number of granules per unit cytoplasmic volume were minor (+ 40%) in comparison to the increase in volume density. The distribution of granule diameter was roughly normal and unimodal at each time interval, and the increase in average diameter over time was marked by an increase in the upper limit of the size distribution and an increased percentage of large granules. The size of condensing vacuoles also increased during this period, and their distributions were roughly coextensive with those seen for zymogen granules at the same time. The potential origins of changes in granule size are discussed, as well as the important effect that size has on the number of granules observed in "two-dimensional" tissue sections viewed in the electron microscope. If size is not considered in our estimates, then we underestimate the numerical density in cells with small granules compared to those with large granules. The results indicate the central role of granule size, as opposed to number, in determining granule volume density in the embryonic pancreas.

Animals↗
PubMed1981

Zymogen granules of pancreas decrease in size in response to feeding.

In the first descriptions of pancreatic enzyme secretion about 100 years ago, it was noticed that zymogen granules became smaller and disappeared from the apical region of acinar cells after feeding. We have repeated these experiments and characterized changes in granule size by quantitative electron microscopy 90 min after feeding previously fasted rats. In fasted animals, granules occupied the apical portion of the cell, had an average number of 45 +/- 3 granules per cell section (+/- SE), and measured 0.85 +/- 0.15 micrometers in diameter (+/- SD). After feeding, the number and size of granules decreased. Individual samples showed either a decrease in size alone or a decrease in both size and number, but in no case did they show a reduction in granule number alone. The mean diameter of granules decreased to 0.65+/- 0.15 microns (+/- SD) or about a 55% reduction in average granules volume as compared to controls (0.32 vs. 0.14 microns 3). The size distributions were unimodal and normal in both fasted and fed rats; however, in fed animals, the distribution was shifted to lower values (diameter range 0.40-1.40 microns for fasted rats vs. 0.10-1.30 microns for fed rats). The number of granules decreased to an average of 29 +/- 2 granules per cell section (+/- SE) after feeding, and, on the average, samples with the most granules had larger ones than samples with the fewest granules. The present results support the original observations on live rabbit pancreas that individual granules decrease in size in response to feeding. We suggest that these size changes reflect the loss of proteins across the granule membrane as proposed by the equilibrium hypothesis for digestive enzyme secretion.

Animals↗
PubMed1977

Glycogen deposits in the pyloric gland of the ascidian Styela clava (Urochordata).

The pyloric gland of Styela clava contains large glycogen deposits that are digested by treatment with alpha amylase and depleted by 15 days starvation. The deposits are surrounded by cytoplasmic regions containing smooth endoplasmic reticulum and mitochondria. The cells also have rough endoplasmic reticulum, Golgi cisterns, lysosomes, microvilli, cilia, and lateral infoldings of the plasma membrane. The fine structure of the pyloric cells and the position of tubules between the absorptive epithelium and general circulation suggest that the gland functions as the vertebrate liver in carbohydrate metabolism. The pyloric cells of Styela do not appear to be excretory in a "renal" sense, since there is no infolding of the basal plasmalemma and mitochondria are usually associated only with the glycogen deposits. However, a hepatic-like excretory role is consistent with current findings. In light of the phylogenic affinities of vertebrates and ascidians, it is possible that the pyloric gland is homologous to the liver.

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