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The effect of 2-acetyl-4-tetrahydroxybutylimidazole on lymphocyte subsets in peripheral blood of the rat.

A constituent of Ammonia Caramel, 2-acetyl-4-tetrahydroxybutylimidazole (THI), is known to cause a reduction in the number of circulating lymphocytes when fed to rats. In the present study the effect of giving THI 1 mg/kg by gavage daily for 7 days on the numbers of lymphocytes in subsets has been monitored in peripheral blood. Both immunoglobulin light chain-bearing B-cells (MARK-1+) and CD5 marker-bearing T-cells (OX-19+) were reduced in number within 1 day of treatment. Within the pan-T-cell population, Class II MHC reactive helper T-lymphocytes (W3/25-) were more reduced than the Class I MHC reactive cytotoxic/suppressor T cells (OX-8+). The number of null cells (MARK-1-, OX-19-) was not affected; the majority of these cells appeared to be large granular lymphocytes.

Animals↗

Immunodynamics of minimal change nephrotic syndrome in adults T and B lymphocyte subsets and serum immunoglobulin levels.

Thirty-two adult patients with minimal change nephrotic syndrome (MCNS) were studied in order to clarify the characteristics of the immune system in MCNS and their relation to clinical activity. In the active phase (n = 17), serum immunoglobulin (Ig) M and E levels, B lymphocytes (surface Ig-positive cells) and their subsets, surface IgG, IgM and IgE positive cells; B gamma, B mu and B epsilon, were increased, whereas the serum IgG level and OKT3-reactive cells, peripheral T lymphocytes; T3, were decreased. In the remitted phase maintained by steroid therapy (n = 17), serum Igs and B lymphocyte subsets tended to return to normal levels concomitant with decreases in T3 and T4, and an increase in T8 in consequence of a marked decrease in T4/T8 (helper/suppressor) ratio. In stable remission continuing with no steroid therapy (n = 14), the above abnormalities returned to normal ranges, except for serum IgM which remained at a high level and re-elevated serum IgE. These results suggest that immunological abnormalities in MCNS are characterized by acceleration of the IgE and IgM producing systems and impaired maturation of the IgG producing system despite normal differentiation from the IgM producing to IgG producing system, possibly caused by T lymphocyte dysfunction.

Adolescent↗

Lymphocyte subsets in the endometrium of genitally normal mares and mares susceptible to endometritis.

The density and distribution of MHC Class II positive cells and subpopulations of lymphocytes were studied in the endometrium of genitally normal mares and mares susceptible to endometritis. In genitally normal mares, more MHC Class II positive cells were present in the epithelium and stratum compactum during oestrus than dioestrus. Significantly more CD4+ and CD8+ lymphocytes were present in the stratum compactum than in the stratum spongiosum. CD4+ lymphocytes were present in greater numbers than CD8+ lymphocytes in the stratum compactum but approximately equal numbers were present in the stratum spongiosum and in lymphoid aggregates. Occasional CD4+ and CD8+ cells were seen in the luminal and glandular epithelium. Infrequently, B cells were present in the endometrium and were not observed in the epithelium. Numbers of T and B cells did not appear to be affected by cycle stage. In mares with endometritis, the densities of CD4+, CD8+ and B cells were significantly increased. Large aggregates of lymphoid cells which contained approximately twice as many CD4+ cells as CD8+ cells were present in the endometrium of these mares and all 3 subclasses of lymphocyte were seen occasionally in luminal and glandular epithelium.

Animals↗

Identification of gamma delta T lymphocyte subsets that populate calf ileal mucosa after birth.

Ileal intraepithelial and lamina propria lymphocytes from newborn, 1.5-week-old, and 3-week-old calves were compared to determine to what extent the mucosa becomes populated after birth. Single and dual fluorescence flow cytometry were used with monoclonal antibodies to bovine (Bo) CD molecules to identify lymphocyte subpopulations. Few ileal mucosal lymphocytes were present in calves at birth. However, by 1.5 weeks of age, the villi were populated with large numbers of lymphocytes, and by 3 weeks of age, the numbers had increased further. These included a prominent subpopulation of gamma delta T cells. Several subsets of gamma delta T cells populated ileal mucosa after birth. The predominant subset coexpressed BoCD2, and a smaller subset coexpressed BoCD8. WC1+ gamma delta T cells comprised the smallest subset. All gamma delta T cell subsets coexpressed ACT2, a molecule expressed on activated WC1+ and WC1- gamma delta T cells from cattle.

Animals↗

Characterization by monoclonal antibodies of lymphocyte subsets present in B-enriched suspensions.

B lymphocyte enriched suspensions isolated by E rosette depletion (E-cells) or by nylon fiber adherence (adherent cells) were identified by their cellular composition using different T and B cell markers (SIg,E receptor, T3, T4, T8 and Ia-like antigens). The cells were isolated from peripheral blood both of healthy donors and uremic dialysis patients. A variable proportion of non-B cells was found in some preparations. This contaminant was represented mainly by Null cells in E-lymphocyte suspensions and by T cells in the adherent population. Contaminating T lymphocytes were most frequently found in adherent cell preparations from uremic individuals and appeared to be an heterogeneous population including variable proportions of T4, T8 and Ia positive T cells. A significant increase of T8+ cells and a decrease of the ratio T4/T8 was seen among adherent T cells as compared to the normal distribution among T peripheral lymphocytes.

Antibodies, Monoclonal↗

Effect of hemodialysis on T lymphocyte subsets, con-A-activated suppressor cell activity, and interleukin-2 receptor expression on lymphocytes in chronic uremic patients.

Effect of hemodialysis (HD) on some indices of immune response was studied in nine chronic uremics. Total lymphocyte, OKT4+, and OKT8+ cell numbers significantly decreased during the first 20 min of HD, and they were decreased till the third hour of the procedure, whereas the OKT4+/OKT8+ cell number ratio did not change significantly. Before HD, Con-A--activated suppressor cells exerted a stimulatory action on autologous responder cells measured in two-step culture. During HD, Con-A-activated suppressor cell activity transiently appeared, with its peak at 60 min after the start of HD. It was accompanied by a transient rise in lymphocyte count with spontaneous interleukin-2 (IL-2) receptor expression, whereas the number of cells expressing IL-2 receptor following phytohemaglutinin (PHA) stimulation was progressively decreased during HD. A significant correlation was found between the increment of Con-A-activated suppressor cell activity and the increment of spontaneous IL-2 receptor expression on lymphocytes during one single blood flow through the dialyzer. The results supply further evidence that HD may impose additional disturbances on immune regulation in chronic uremics.

Adult↗

Demonstration of a CD3+ lymphocyte subset in the epidermis of athymic nude mice. Evidence for T cell receptor diversity.

The existence of CD3/TCR-bearing lymphocytes in athymic and thymectomized chimeric mice implies that T cell maturation can occur in the absence of a thymus. Considering the possibility that the epidermis may be one of the organs providing T cell educating stimuli, we attempted to characterize the Thy-1+ epidermal lymphocyte population of athymic mice. Immunohistologic studies of epidermal sheets revealed (1) that Thy-1+ epidermal cells of C57BL/6 nu/nu mice are CD5-, CD4-, and predominantly CD8-, and (2) that a minor subset of these cells displays anti-CD3 epsilon reactivity. Although these CD3+ epidermal cells could hardly be detected at 6 wk of age, they comprised approximately 2% of all Thy-1+ epidermal cells in 12-mo-old athymic mice. Most of these CD3+ cells expressed TCR-gamma/delta, but TCR-alpha/beta+ cells were also present. TCR-gamma/delta+ epidermal T cells of athymic mice preferentially expressed TCR V gamma 2, V gamma 4, and V gamma 5 specificities rather than TCR V gamma 3 as found on DETC of euthymic mice. Using mitogenic stimuli, we have succeeded in establishing cell lines and clones from BALB/c nu/nu and C57BL/6 nu/nu epidermis. Their marker profile corresponds to that seen on resident CD3+ epidermal cells, as well as on a very small subset of CD3+ splenic and lymph node lymphocytes of athymic mice. The ontogenetic relationship, if any, between the epidermal and lymphoid CD3+, CD5-, CD4-, CD8- cells, has yet to be clarified. Cell lines/clones representative of resident CD3+ epidermal cells of nu/nu mice should provide a useful tool in the elucidation of homing patterns and functional properties of extrathymically matured T cells.

Age Factors↗

T lymphocyte subsets and cytokine production by graft-infiltrating cells in FSGS recurrence post-transplantation.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) aetiology remains undefined although a derangement of lymphocytes and monocytes macrophages, at least, has been strongly suspected. We report the graft-infiltrating phenotypes and their cytokine production in a case of FSGS recurrence post-transplantation. METHODS: The kidney transplant recipient suffered immediate FSGS recurrence. Aspiration biopsies were done at the first and second week post-surgery and were analysed by flow cytometry. The cytokine analysis was done on aspiration sample culture supernatants and serum by enzyme-linked immunosorbent assay. RESULTS: High expression of CD3CD69, CD3CD71 and CD4CD29 was found on infiltrating lymphocytes. Biopsy cultures pointed to a Th0/Th1 pattern of cytokine production as well as significant synthesis of transforming growth factor-beta1. Interestingly, monocyte chemokines were absent. CONCLUSION: We report evidence of intragraft lymphocyte activation in the early days of FSGS recurrence. Aspiration biopsy cultures showed failure of cyclosporin A to inhibit interleukin-2 (IL-2) production by infiltrating lymphocytes. If our findings are confirmed in similar patients, a trial with anti-IL-2-receptor antibody could be warranted.

Adult↗

Large granular lymphocytosis, lymphocyte subset inversion, thrombocytopenia, dysproteinemia, and positive Ehrlichia serology in a dog.

A 7-year-old, mixed-breed dog was presented for evaluation of a possible lymphocytic leukemia. Results of laboratory testing included thrombocytopenia, large granular lymphocytosis, inverted CD4:CD8 ratio, hyperglobulinemia, and hypoalbuminemia. Results of a tick-borne disease panel indicated a positive immunoglobulin G serum titer (1:2,048) to Ehrlichia canis, supporting exposure to this organism. The dog responded to a combination treatment of doxycycline and prednisone. A review of the literature and novel diagnostic methods that aided in the diagnosis of this case are discussed.

Animals↗

Lymphocyte subsets in normal human lymphoid tissues.

A series of B, T, natural killer (NK) cell, and monocyte-specific monoclonal antibodies was used to determine the localization of lymphocyte subpopulations in frozen tissue sections of human lymph node, spleen, tonsil, and thymus by means of an immunohistochemical technic. In thymus, most cortical thymocytes reacted with Leu 1, Leu 2a, Leu 3a, Leu 4, Lyt 3, OKT3, and OKT6 antibodies. Except for OKT6, Leu 2a, and Leu 3a, these antibodies also reacted with medullary thymocytes. The majority (70-80%) of medullary thymocytes reacted with Leu 3a and a smaller fraction (20-30%) with Leu 2a antibody. The staining pattern of thymic medulla approximates the staining pattern of peripheral T cells. In peripheral lymphoid tissues, the majority of cells in the paracortical region of lymph node and in the periarteriolar sheath of spleen stained with Leu 1, Leu 4, OKT3, and Lyt 3 antibodies. Staining with Leu 3a and Leu 2a identified 60-80% and 20-40% of total T cells, respectively, as defined by Lyt 3 positivity. In addition, a substantial number of Leu 3a+ and Leu 7+ cells were found in the germinal centers of secondary follicles. This finding supports the importance of these subsets of lymphocytes in regulation of the human immune response. Leu 2a+ cells were rare in tissues with prominent follicular hyperplasia, but appeared in considerable number in the red pulp of spleen. In the mantle zone of lymphoid follicles, the majority of lymphocytes were positive for IgM, IgD, and B1. Approximately 60-70% of these cells bore kappa chain and 30-40% lambda chain immunoglobulin. The extracellular substance in germinal centers was positive for B1, IgG, IgM, kappa, and lambda. The majority of germinal center cells appeared to contain no surface or cytoplasmic immunoglobulins. Small mononuclear cells bearing OKM1 marker were abundant in the marginal zone of white pulp and in the red pulp of spleen but, rarely were observed in other portions of lymphoid tissues. OKM1 also reacted with granulocytes. Leu 7+ (NK) cells were rare in the thymus, but frequent in the GC of secondary follicles. The distribution of Leu 7+ cells did not correspond to staining with Lyt 3 and Leu 2a.

Antibodies, Monoclonal↗