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H N Claman

Publications and source records attributed to H N Claman.

At least 55 records · Page 3Linked to original sources
PubMed1987

Cutaneous mast cell depletion and recovery in murine graft-vs-host disease.

Mast cells as studied by light microscopy with metachromatic staining, have been noted to "disappear" from the skin of mice with chronic graft-vs-host disease (GVHD) produced across minor histocompatibility barriers. This mast cell disappearance is accompanied by ultrastructural evidence of loss of granule contents. In this study, we followed cutaneous mast cells in chronic GVHD over 9 mo by three methods: Light microscopy of toluidine blue-stained sections showed that mast cells not seen at day 42 reappeared between days 94 and 125, were supramaximal at days 146 and 164, and returned to normal levels at days 195 and 280. Double immunofluorescent staining of mast cells for the presence of surface IgE receptors and cytoplasmic granules (avidin) revealed IgE receptor-bearing cells that lacked avidin-binding granules at the time when mast cells were not apparent on light microscopy. By electron microscopy, reappearing mast cells have the morphology of immature dermal mast cells. Ultrastructural abnormalities of mast cells persist some 150 days after GVHD induction. The possible relationship of these mast cell changes to the development of dermal fibrosis in chronic GVHD is discussed.

Animals↗
PubMed1987

Simultaneous in situ detection of IgE receptors and cytoplasmic granules in murine cutaneous mast cells.

A method is described for the simultaneous in situ detection of surface receptors and cytoplasmic granules in mast cells of frozen sections of mouse skin. Surface IgE receptors are detected after saturation of the receptors with a murine monoclonal antibody of IgE isotype. The latter is subsequently detected by monospecific rabbit anti-mouse IgE (purified on protein A-Sepharose) followed by FITC-conjugated goat anti-rabbit IgG. Cytoplasmic granules are localized by staining with TRITC-avidin conjugate. Normal cutaneous mast cells show green surface fluorescence and red intracellular granules. The method is specific for mast cells; other cells with Fc receptors for IgE are not seen. This method should be useful in the study of situations in which mast cells may have become degranulated.

Animals↗
PubMed1987

Monoclonal antibody analysis of skin in chronic murine graft vs host disease produced across minor histocompatibility barriers.

Chronic graft vs host disease (GVHD) across minor histocompatibility barriers was produced in BALB/c mice by the injection of spleen cells from B10.D2 mice. Changes in the skin were analyzed in frozen sections using a panel of monoclonal antibodies detected by immunoperoxidase methods. Compared to control animals, a number of changes occurred in the skin of animals with chronic GVHD. In the epidermis, there were increased numbers of Thy-1-positive dendritic cells; keratinocytes expressed Thy-1 and Ia antigens. T lymphocytes appeared in both dermis and epidermis. In the early stages, cells with "helper" and "suppressor" phenotypes were present, while at later times "helper" cells remained in the epidermis and "suppressor" cells remained in the dermis. Cells bearing markers of macrophages were prominent in both dermis and epidermis after the second week. Of great interest was the appearance of spindle-shaped cells in the dermis which expressed Thy-1 and Ia. These cells resembled fibroblasts which may be activated to produce the excess collagen seen in the skin of chronic GVHD.

Animals↗
PubMed1987

Corticosteroids in inflammatory bowel disease. A review.

Corticosteroids have been used for decades in the treatment of inflammatory bowel disease. Despite considerable information on the clinical response to corticosteroids in inflammatory bowel disease, much less is known concerning corticosteroids' effects on the underlying immunopathology of the disease. In this review, we discuss the known immunologic actions of corticosteroids: their effects on eicosanoid production and on modulating the humoral and cellular immune response. After reviewing the postulated immunological aberrations in inflammatory bowel disease, we speculate on the specific immunologic effects of corticosteroids in this disease.

Adrenal Cortex Hormones↗
PubMed1986

Natural suppressor activity in graft-vs-host spleen and normal bone marrow is augmented by IL 2 and interferon-gamma.

Natural suppressor (NS) cells isolated from the spleens of mice 34 or more days after induction of chronic graft-vs-host disease showed potent suppressor activity that was dependent on the presence of lymphokines such as those found in lectin-free Con A supernatant (CAS). Both IL 2 and IFN-gamma were found to enhance NS activity, with IFN-gamma being the most active molecule. To generalize these findings, normal adult bone marrow (BM), a second environment where NS activity has been reported, was examined. Normal adult BM cells nonspecifically suppressed both B and T cell mitogen responses. BM suppression could also be enhanced by the addition of CAS to the cultures. Removal of plastic-adherent cells, Thy-1.2-positive cells, or B cells did not significantly diminish suppression or remove the ability to enhance suppression with CAS. When isolated on discontinuous Percoll gradients, BM suppressor cells banded in the less dense fractions, and the suppression in these bands was also enhanced by lymphokines. The suppressive activity of these cells was greatly enhanced by the addition of CAS, IFN-gamma, or IL 2. However, IFN-gamma appears to be a more potent enhancing molecule, being active at levels between 1 and 10 U/ml.

Animals↗
PubMed1986

Mast cell "disappearance" in chronic murine graft-vs-host disease (GVHD)-ultrastructural demonstration of "phantom mast cells".

Mast cells were studied during the induction of chronic graft-vs-host disease (GVHD) induced in mice across minor histocompatibility barriers. B10.D2 spleen cells (or control BALB/c cells) were injected into irradiated (600 rad) BALB/c recipients. Serial skin biopsies were taken over 26 days, during which time changes occurred resembling scleroderma, namely, dermal fibrosis, a mononuclear cell infiltrate, and loss of fat and appendages. Mast cells, when stained with toluidine blue, "disappeared" from GVHD, but not from control skin. Ultrastructural analysis showed that mast cells in GVHD skin were indeed present but underwent degranulation. Some mast cells showed only pale expanded sacs, indicating granule depletion. Because these cells could not be seen by toluidine blue staining but were plainly present, we have called them "phantom mast cells." Cellular activation occurred in many GVHD mast cells as shown by increased cytoplasmic activity, with numerous Golgi complexes, ribosomes, granular endoplasmic reticulum, and small vesicles. No identifiable mast cells were seen after day 19. No significant changes were seen in the mast cells of syngeneic control mice. We believe that immunologic processes in chronic GVHD cause a slow release of mast cell granule contents, which is different from anaphylactic degranulation. The depleted mast cells (invisible by toluidine blue staining) are also activated, perhaps in an attempt to replete their stores of granule contents. We discuss the relation of mast cell changes to fibrosis.

Animals↗
PubMed1986

Antibody-mediated regulation of T cell responses. I. Characterization of a monoclonal antibody which specifically regulates contact hypersensitivity to DNFB in BALB/c mice.

Contact hypersensitivity (CS) to 2,4-dinitrofluorobenzene (DNFB) in BALB/c mice is regulated by autoanti-idiotypic antibody. This report describes the preparation and characterization of a monoclonal antibody, 2-16.1, which has characteristics previously described for the serum anti-idiotypic antibodies. Monoclonal 2-16.1 was prepared by fusing lymph node (LN) cells from optimally sensitized BALB/c mice to the P3X myeloma. The monoclonal product of the cloned hybridoma is an IgM (K) immunoglobulin which does not bind to DNP-protein but which does bind to other immunoglobulins with anti-DNP specificity, primarily of the IgM class. Functionally, 2-16.1 inhibits the efferent limb of the CS reaction as measured by passive transfer of immunity. This inhibition is antigen-specific and appears to require the presence of a subset of Ia+ T cells in the DNFB-immune LN cell population. Suppression of transfer of immunity is strain-specific. Finally, suppression occurs only in the absence of complement, indicating that a lytic mechanism is not involved and that 2-16.1 does not recognize determinants expressed on the effector T cells of the CS reaction. Collectively, these results indicate that 2-16.1 is a monoclonal anti-idiotypic antibody, and that the hybridoma CSDNP 2-16.1 represents a clone of B cells which is stimulated during the primary CS response to DNFB and whose antibody product is involved in the endogenous, active regulation of this T cell-mediated response.

Animals↗
PubMed1986

Desensitization of contact allergy to DNFB in mice. III. Characteristics of immediate desensitization induced by haptenated spleen cells.

The immediate effects and mechanisms of desensitization of contact sensitivity to dinitrofluorobenzene (DNFB) were investigated. Intravenous injection of dinitrophenol (DNP)-labeled syngeneic spleen cells caused significant antigen-specific inhibition (greater than 40%) of the contact response within 24 hr in mice that had been sensitized 2 weeks prior to desensitization. With low concentrations of the hapten used for labeling, allogeneic spleen cells were found to be more efficient than syngeneic ones in inducing the down-regulation of the contact response. The most efficient desensitization was produced by DNP-cells that differed from the recipient at the MLS locus. Haptenated spleen cells induced the production of suppressor mechanisms, as spleen cells from animals desensitized with DNP-cells were able to down-regulate recipients in adoptive transfer and could block the passive transfer of contact sensitivity. Procedures that interfere with the development of suppressor cells, e.g., cyclophosphamide and adult thymectomy, interfered with desensitization by DNP-cells. These results are in contrast to desensitization with soluble dinitrobenzenesulfonic acid (DNBS), where suppressor mechanisms have not been shown. The mechanisms for desensitization depend upon the form of the desensitizing antigen.

Animals↗
PubMed1985

Synergism between T and non-T cells in the in vivo induction and in vitro expression of graft-vs.-host disease-induced natural suppressor cells.

We have been studying the mitogen hyporesponsiveness and immunosuppression induced in chronic murine graft-vs.-host disease (GVHD) induced across minor histocompatibility (MiHA) barriers. In this system, donor and recipient mice are major histocompatibility complex- and mls-identical, and are nonreactive in primary mixed leukocyte reactions. Spleen cells from B10.D2 (H-2d, mls b) mice were injected into irradiated (600 rad) BALB/c (H-2d, mls b) recipients. Recipient spleen cells are hyporesponsive to mitogens, and contain natural suppressor (NS) cells. We investigated the cellular requirements for both the in vivo induction and the in vitro expression of this GVH suppression. T cells are required in the graft, but they are not sufficient to induce suppression, and a non-T cell population is also required for maximum induction in vivo. T cells are also required for the maximum expression of NS cell suppressive ability in vitro. Early in the course of GVH, the suppressor cells are able to suppress the Con A and LPS response of all mouse strains tested (except for the relative difficulty in suppressing the B10.D2 LPS response). Later, they become almost completely unable to suppress the B10.D2 LPS response; while still being able to suppress the Con A and LPS response of all other strains tested (including the B10.D2 Con A response). This inability to suppress a B10.D2 LPS response can be brought back to almost complete suppression by the addition of concanavalin A supernatant (CAS). We present a hypothesis to explain what may be a common mechanism for GVH-induced suppression, total lymphoid irradiation-induced suppression, and neonatal tolerance. These situations all include rapidly proliferating lymphohematopoietic stem cell populations, and also have large numbers of NS cells. NS cells can suppress proliferating lymphoid populations, and their development and activity are greatly enhanced by T cell signals such as are supplied by donor T cells in chronic GVHD. Thus, NS cells may feed back on and downregulate self-reactive T cells or T cells responding to introduced foreign antigens.

Animals↗
PubMed1985

Chronic graft-versus-host disease as a model for scleroderma. II. Mast cell depletion with deposition of immunoglobulins in the skin and fibrosis.

We explored the pathologic changes in the skin of mice undergoing a chronic graft-versus-host (GVH) reaction. In rodents and in man, chronic GVH includes the deposition of excess collagen in the skin-a reaction which resembles idiopathic scleroderma. GVH disease across minor histocompatibility barriers was produced by injecting B10.D2 cells into irradiated BALB/c mice. These strains are identical at the H-2 and Mls loci but differ in minor histocompatibility antigens. Control BALB/c mice received irradiation and BALB/c cells. Serial skin biopsies were taken and studied for histological changes characteristic of chronic GVHD, for mast cell density, and for the deposition of immunoreactants. GVHD was produced in B10.D2----BALB/c mice as measured by body weight loss and the production of skin changes including dermal fibrosis, loss of fat and appendages, and a mononuclear cell infiltrate. Dermal mast cells, assessed by toluidine blue staining, were normal at Day 11, but had disappeared by Days 21-63 and returned to normal by Day 104. Immunoglobulins IgG, IgA, and IgM appeared at the dermo-epidermal junction and along the basement membrane zone of hair follicles. This deposition was maximal at Day 42 and waned thereafter. Thus the appearance of immunoglobulins in the skin was maximal when mast cell staining was minimal. The changes in this GVHD model leading to a scleroderma-like picture in the skin are compatible with an immune etiology for the fibrosis. Vasodilation following liberation of mast cell mediators would facilitate the deposition of immunoglobulins. The disappearance of mast cell staining may be caused by extensive degranulation. We postulate an interaction between GVHD-activated T cells, mast cell stimulation, fibroblast activation, and fibrosis.

Animals↗
PubMed1985

The effect of histamine receptor antagonists on specific and nonspecific suppression of experimental contact sensitivity.

We studied the effects of H1 and H2 histamine receptor antagonists on down regulation of contact sensitivity (CS) to dinitrofluorobenzene (DNFB). Two H2 receptor antagonists, cimetidine and ranitidine, reversed the nonspecific immunosuppression of CS induced by burns. On the other hand, these two drugs did not affect the antigen-specific suppressor T cell-mediated tolerance to DNFB induced by dinitrobenzene sulfonic acid. Two H1 antagonists did not affect the down regulation of CS induced by either tolerance or burning. The differential sensitivities to histamine 2-receptor antagonists indicate that the mechanisms for nonspecific burn-induced immunosuppression are different from those for hapten-specific tolerance to DNFB.

Animals↗
PubMed1985

Restoration of immunity in burned mice by cimetidine.

We have previously described a mouse model of postburn suppression of cell-mediated immunity (CMI). Ear swelling (ES) in response to contact antigen challenge is depressed maximally 14 days following a 25% steam burn and recovers to control levels 3 weeks postburn. Splenic lymphocyte proliferation in response to Concanavalin A (Con A) is also depressed 14 days postburn. Splenic T-lymphocyte subset analysis with monoclonal antibodies for helper cells (Lyt 1.2) and suppressor cells (Lyt 2.2) reveals that T-helper cells reach a minimal level and T suppressor cells reach a maximum level 14 days postburn. The helper: suppressor ratio (HSR) reaches its nadir at day 14. Treatment of burned mice with low-dose cimetidine (2 or 10 mg/kg/day), but not high-dose (50 mg/kg/day), for 14 days restores CMI. Low-dose cimetidine also normalizes the HSR but does not effect postburn depression of mitogen responsiveness. Low-dose cimetidine probably restores CMI by inhibiting suppressor cells, whereas high doses provide more global inhibition. Recovery of mitogen responsiveness may require continued cimetidine presence in culture.

Animals↗