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D T Umetsu

Publications and source records attributed to D T Umetsu.

84 records · Page 5Linked to original sources
PubMed1986

Antigen presentation by human dermal fibroblasts: activation of resting T lymphocytes.

We have shown that human dermal fibroblasts, exposed to interferon-gamma (IFN-gamma) to induce surface class II major histocompatibility complex (MHC) antigens, were capable of presenting tetanus toxoid (TT) antigen to human TT-specific T cell clones. Antigen presentation by fibroblasts was antigen dependent, required HLA-DR expression by fibroblasts, and was MHC restricted. In contrast, we now report that IFN-gamma-treated fibroblasts are unable to present TT antigen to purified resting T cells obtained from the peripheral blood of TT-immune donors. In addition, although IFN-gamma-treated fibroblasts were able to stimulate alloreactive T cell clones, they were unable by themselves to stimulate primary allogeneic responses in resting T cells. The failure of fibroblasts to stimulate resting T cells was not due to suppressor effects by fibroblasts, because induction of TT and alloantigen responses in resting T cells by monocytes was not inhibited by the presence of fibroblasts. On the contrary, IFN-treated fibroblasts were synergistic with small numbers of monocytes in activating resting T cells. In addition, the failure of antigen presentation by fibroblasts to resting T cells was reversed by the addition of recombinant human interleukin 2 (rIL 2) to cultures, but not of purified human interleukin 1 (IL 1). These results emphasize that the requirements for activation of resting T cells differ from those of T cell clones. Although fibroblasts can efficiently present antigen to T cell clones, antigen presentation by fibroblasts to resting T cells requires the addition of exogenous IL 2. It is postulated that fibroblasts differ from classical antigen-presenting cells in that fibroblasts are incapable of stimulating the production of IL 2 in resting T cells.

Adult↗
PubMed1985

Recurrent sinopulmonary infection and impaired antibody response to bacterial capsular polysaccharide antigen in children with selective IgG-subclass deficiency.

We studied 20 children with recurrent sinopulmonary infections and serum IgG levels within the normal range, who had selective IgG-subclass deficiency. Twelve of the children were IgG2 deficient, five were IgG3 deficient, and three were deficient in both IgG2 and IgG3. IgA deficiency was present in 3 of the 20 patients. In the children with IgG2 deficiency, serum antibody concentrations to the capsular polysaccharide of Hemophilus influenzae type B (Hib) were significantly lower than those in age-matched controls, both before and after immunization with the Hib capsular polysaccharide antigen, which elicits antibody predominantly of the IgG2 subclass. In contrast, their serum antibody titers to the tetanus and diphtheria toxoid protein antigens, which elicit antibody predominantly of the IgG1 subclass, were normal in comparison with those of age-matched controls. These results suggest that impairment of the antibody response to specific microbial antigens predisposes patients with selective IgG-subclass deficiencies to recurrent infections. Thus, as an aid in determining therapy, children with recurrent infections and normal total serum IgG should be evaluated for this condition.

Adolescent↗
PubMed1985

Differential requirements of B cells from normal and allergic subjects for the induction of IgE synthesis by an alloreactive T cell clone.

Human T cell helper/inducer clones were used to induce IgE synthesis in B cells from both allergic and nonallergic donors. An alloreactive T cell clone, activated by recognition of specific HLA-DR antigens, stimulated peripheral blood B cells from both allergic and nonallergic donors to synthesize IgE antibody. B cells of allergic donors differed from those of nonallergic donors in their requirements for induction of IgE synthesis. Induction of IgE synthesis in B cells from nonallergic individuals occurred only under conditions of cognate interaction, in which the B cells expressed the alloantigen recognized by the T cells. In contrast, IgE synthesis in B cells from allergic donors occurred under conditions of cognate interaction with T cells as well as bystander conditions where the B cells did not express the alloantigen recognized by the T cell clones and where the T cell clones were stimulated by third-party monocytes bearing the relevant alloantigens. Furthermore, bystander stimulation of IgE synthesis in allergic donors occurred in the presence of tetanus toxoid (TT) antigen-specific T cell clones activated by the appropriate TT-pulsed monocytes. In contrast to the differing requirements of B cells from normal vs. allergic subjects for the induction of IgE synthesis, these B cells did not differ in their requirements for the induction of IgG synthesis. IgG synthesis was induced in all B cells under conditions of cognate interaction with the T cells as well as under conditions of bystander stimulation. These results suggest that cognate T-B cell interactions may be important in the development of IgE immune responses in the normal host.

Adult↗
PubMed1985

HLA-DR-4-associated alloreactivity of an HLA-DR-3-restricted human tetanus toxoid-specific T cell clone: inhibition of both reactivities by an alloantiserum.

We present here the first report of a human helper/inducer T cell clone (F6) that specifically recognizes tetanus toxoid (TT) in the context of self-major histocompatibility complex (MHC) determinant(s) (HLA-DR3), and in addition recognizes a specific but unrelated MHC determinant(s) in the absence of conventional antigen. Extensive subcloning insured that the cells were progeny of a single cell. Furthermore, removal of the cells proliferating to the alloantigen with bromodeoxyuridine and light removed cells responding to both TT plus self-MHC and to the stimulating alloantigen, again indicating that F6 was the progeny of a single cell. The alloantigen recognized by this TT-specific clone appears to be closely linked to HLA-DR4 since cells from 13 of 14 HLA-DR4+ donors stimulated F6. An antiserum which recognizes HLA-DR4, when added to cultures, blocked the alloreactivity of F6, and in addition blocked its proliferation to TT plus HLA-DR3. Absorption of this antiserum with HLA-DR4+ cells or with TT-pulsed HLA-DR3+ cells removed its capacity to inhibit the proliferation of F6. These results suggest that the antigen recognition unit on F6 is stimulated both by allodeterminants expressed on HLA-DR4 cells and by TT plus HLA-DR3. These moieties cross-react at the T cell recognition level as well as at the antibody level.

Clone Cells↗
PubMed1985

Serum sickness triggered by anaphylaxis: a complication of immunotherapy.

An 8-year-old boy developed anaphylaxis after receiving his maintenance dose of immunotherapy and proceeded to display the signs and symptoms of serum sickness. These consisted of fever, arthralgia, arthritis, urticaria followed by a hemorrhagic palpable rash, edema, lymphadenopathy, splenomegaly, abdominal pain, proteinuria, and neurologic manifestations consistent with vascular compromise of the posterior cerebral circulation. A skin biopsy specimen revealed perivascular infiltrates of lymphocytes and few polymorphonuclear neutrophils. The timing of events in this patient suggests that immunotherapy initiated a chain of events beginning with anaphylaxis and leading to serum sickness. It is hypothesized that the enhanced vascular permeability that accompanied the anaphylaxis allowed immune complexes that may have preexisted in the circulation to deposit in the blood vessels of the patient. These complexes may or may not have been related to the immunotherapy itself. Because antihistamines are known to prevent the induction of serum sickness, early and aggressive treatment of anaphylaxis during immunotherapy may prevent the occurrence of immune complex disease.

Anaphylaxis↗
PubMed1985

Human dermal fibroblasts present tetanus toxoid antigen to antigen-specific T cell clones.

Cultured human dermal fibroblasts treated with immune interferon express HLA-DR antigens. We report here that DR-positive fibroblasts present tetanus toxoid (TT) to autologous TT-specific monoclonal helper T cells vigorously depleted of monocytes by passage over Sephadex G10 columns followed by treatment with the monoclonal antibodies (mAb) OKM1 and Leu M1 plus complement. The extent of T cell proliferation in response to TT presented by DR-positive fibroblasts was similar to that elicited using monocytes as antigen-presenting cells. The proliferative response was TT dependent, antigen specific, depended upon DR expression by fibroblasts, appeared MHC restricted, and was completely blocked by mouse mAb to HLA-DR but not by mAb to HLA-A,B, or DQ. DR-positive fibroblasts pulsed with TT were similarly effective in antigen presentation. In summary, immune interferon-stimulated human dermal fibroblasts can substitute for classical antigen-presenting cells in antigen-specific proliferative responses. Since fibroblasts are a ubiquitous cell type in the body, they may play a significant role in the immunobiology of the host.

Antibodies, Monoclonal↗
PubMed1983

Ia-restricted interaction between normal lymphoid cells and SJL lymphoma (RCS) leading to lymphokine production. I. Enhancement and suppression of antibody formation to TI antigens by supernatants and cells from cocultures of RCS and lymphoid cells.

Addition of gamma-irradiated reticulum cell sarcoma (RCS) cells causes suppression of the antibody response to trinitrophenyl (TNP)-keyhole limpet hemocyanin (KLH)-primed syngeneic SJL spleen cells to TNP-polyacrylamide (PAA) in vitro. The response of anti-brain antigen (BAT) + C-treated spleen cells is not suppressed by gamma-RCS, but is suppressed by cells from 48-hr SJL lymph node or thymus + gamma-RCS cultures. Addition of as few as 2.5 x 10(5) cultured (anti-I-A + C treated to remove gamma-RCS) cells causes significant inhibition of the responses of both syngeneic and allogeneic spleen cells. Treatment of gamma-RCS-induced suppressor cells with anti-BAT + C reduces their suppressive activity. In contrast to the cells, supernatants (SN) from (lymph node (LN) + gamma-RCS) cultures greatly enhance, in an antigen-dependent fashion, the responses of untreated or anti-BAT + C-treated Sephadex G10-passed spleen cells to TNP-PAA. TNP-SIII polysaccharide, or TNP-Ficoll, but not as much to TNP-KLH. Addition of SN as late as Day 3 of culture still causes about half as much enhancement as leaving SN in throughout the culture period, but it has no effect if left with the spleen cells for only the first day of culture. SN contains high levels of IL-2 and IFN-gamma; absorption with cells from an IL-2-dependent cytotoxic T-cell line removes the enhancing activity, while treatment with pH 2 to remove the IFN-gamma has no effect. SN from an IL-2-producing T-cell line (LBRM-33) has a similar effect on antibody production to TI antigens as does SN of (LN + gamma-RCS). The results suggest a marked dependency of PFC responses to TI antigen on IL-2 in all strains examined, including SJL, LAF1, DBA/2Ha, and CBA/N, probably through a direct activation of B cells. The findings also suggest that suppressor T cells, induced by gamma-RCS in syngeneic lymphoid cells, absorb the IL-2 needed for responses to TI antigens in vitro.

Animals↗
PubMedDate not supplied

When engineered to produce latent TGF-beta1, antigen specific T cells down regulate Th1 cell-mediated autoimmune and Th2 cell-mediated allergic inflammatory processes.

To determine whether T cells which produce large amounts of latent TGF-beta1 are capable of down-regulating autoimmune and allergic disease, myelin basic protein (MBP)-specific and ovalbumin (OVA)-specific BALB/c cloned Th1 cells were transduced with cDNA for murine TGF-beta1 by coculture with fibroblasts producing a genetically engineered retrovirus. The transduced MBP-specific Th1 cells were found to lose the capacity to provoke EAE in BALB/c mice, and to gain instead the ability to protect against EAE in (SJLxBALB/c) F1 mice immunized with proteolipid protein (PLP). This protective effect was not obtained with OVA-specific TGF-beta1 transduced Th1 cells. The transduced OVA-specific Th1 cells did protect against airway hyperreactivity induced by Th2-cell mediated responses to inhaled OVA. This effect was again antigen specific and it also could not be obtained with untransduced OVA-specific Th1 cells. In both cases these effects of antigen specific TGF-beta1 transduced T cells were nullified by administration of neutralizing anti-TGF-beta mAb. Thus, the antigen specificity of the cloned T cells allows the site-specific local delivery of therapeutic active TGF-beta1 to both Th1 and Th2 cell-mediated inflammatory infiltrates.

Animals↗