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T Hamaoka

Publications and source records attributed to T Hamaoka.

At least 181 records · Page 10Linked to original sources
PubMed1989

B cell response pathways regulated by IL-5 and IL-2. Secretory microH chain-mRNA and J chain mRNA expression are separately controlled events.

We have examined the effect of IL-5 and/or IL-2 on the expression of the secretory form of microH chain (microsecond) and J chain mRNA in a homogeneous neoplastic B cell clone, in which proliferation, IL-2R up-regulation and entry into the IgM secretory state are separately controlled events. The IL-5 signal triggers a partial induction of CL-3 cells into the IgM secretory state, characterized by a striking increase of microsecond mRNA expression and an increase in the ratio of the secretory to membrane forms of microH chain mRNA, with a modest increase of J chain mRNA. In contrast, amplification of J chain mRNA is accomplished by the late-acting B cell differentiation stimulus, IL-2, acting on IL-5-pretreated CL-3 cells or acting simultaneously with IL-5 on CL-3 cells. Such dually stimulated cells now are fully induced into IgM secreting cells. These results define the relative roles of IL-5 and IL-2 in B cell differentiation by showing important regulatory effects at the mRNA level. In addition, these results substantiate that appearance of mRNA for J chain, a molecule key to the formation of pentameric IgM, is a limiting factor for high level IgM secretion. The separate control of microsecond and J chain mRNA found in CL-3 cells stimulated with IL-5 and IL-2 elucidates a molecular mechanism by which these two lymphokines synergize in the development of CL-3 cells into IgM secreting cells.

B-Lymphocytes↗
PubMed1989

Thymic stroma-derived T cell growth factor (TSTGF). IV. Capacity of TSTGF to promote the growth of L3T4- Lyt-2- thymocytes by synergy with phorbol myristate acetate or various IL.

The present study investigates the role of thymic stroma-derived T cell growth factor (TSTGF) in promoting the growth of L3T4- Lyt2- (double-negative) thymocytes. Partially purified TSTGF samples were prepared from the culture supernatant of a newly established thymic stromal cell line, MRL104.8a. The TSTGF alone induced only marginal proliferation of double-negative thymocytes, whereas this factor exerted a potent growth-promoting effect on these cells in combination with PMA. Because such an enhanced proliferation was not inhibited by anti-IL-4 or anti-IL-2R antibody, this was not due to the stimulation of an autocrine mechanism involving the production and utilization of IL-4 or IL-2. In scrutinizing PMA-equivalent physiologic substance(s), IL-1 was revealed to be capable of replacing the role of PMA in the above co-stimulation cultures and including enhanced proliferation of double-negative thymocytes in combination with TSTGF. Although TSTGF plus IL-2 or IL-4 also exhibited an appreciable or moderate synergistic effect on the growth of double-negative thymocytes, its magnitude was weaker compared with that obtained by TSTGF plus IL-1. More important, the strikingly enhanced proliferation was induced in the combinations of TSTGF, IL-1, and IL-2 or IL-4 under conditions in which the proliferation induced by IL-1 plus IL-4 or IL-1 plus IL-2 was marginal or slight. Furthermore, such strongly enhanced proliferation was also observed in the double-negative thymocyte population which was additionally depleted of T3+ cells (namely, the L3T4- Lyt-2- T3- or dull population). These results indicate the crucial role of TSTGF in the proliferation of immature thymocytes by synergy with various cytokines.

Adjuvants, Immunologic↗
PubMed1989

Induction of tumor-specific in vivo protective immunity by immunization with tumor antigen-pulsed antigen-presenting cells.

The present study investigates the role of APC in inducing tumor-specific in vivo protective immunity. Thy-1+ cell-depleted, Mac-1+ cell-enriched fraction of normal BALB/c spleen cells were used as a source of APC. These APC were cultured in vitro with the membrane fraction isolated from CSA1M fibrosarcoma derived from BALB/c strain. The administration of such APC into naive BALB/c mice generated the capacity of these animals to reject the subsequently challenged viable CSA1M tumor cells. Although the induction of anti-CSA1M in vivo protective immunity required three consecutive immunizations with more than 10(5) APC which had been pulsed in vitro with 200 to 300 micrograms protein of CSA1M membrane fraction, the immunity was induced irrespective of whether APC were administered via s.c., i.v., or i.p. route. This immunity was tumor-specific, inasmuch as the inoculation of CSA1M or Meth A fibrosarcoma membrane component-pulsed APC resulted in the selective immunity against the challenge with homologous types of tumor cells. The CSA1M-specific in vivo protective immunity was also induced by injecting APC pulsed with solubilized CSA1M membrane components. Moreover, it was demonstrated that the efficiency for inducing anti-CSA1M immunity was much higher in the utilization of tumor Ag-pulsed APC than in the immunization with tumor Ag emulsified in CFA. These results indicate the critical role of APC in generating tumor rejection immunity in vivo and this model presents a novel approach to induce tumor-specific immunity without using tumor cells themselves.

Animals↗
PubMed1989

Enhanced production of interleukin-6 in mice with type II collagen-induced arthritis.

We established an interleukin-6 (IL-6)-dependent cell line from murine plasmacytoma MOPC-104E cells. This cell line (designated PIL-6) was found to respond to murine and to human IL-6, but not to any other cytokines. We used this cell line to investigate the involvement of IL-6 production in type II collagen-induced arthritis in DBA/1 mice. Only marginal IL-6 activity was detected in sera from DBA/1 mice inoculated with Freund's complete adjuvant (FCA) alone, with an unrelated protein (bovine serum albumin) plus FCA, or with type II collagen plus Freund's incomplete adjuvant. However, enhanced IL-6 activity was observed in DBA/1 mice that had been injected with type II collagen plus FCA to induce arthritis. The elevated level of serum IL-6 activity was associated with high levels of IL-6 produced when lymph node cells from arthritic mice were stimulated in vitro with type II collagen. We also found that the L3T4+ T cell subset is responsible for the enhanced production of IL-6 in arthritic mice. The results are discussed in the context of potential roles of IL-6 in the induction and/or expression of chronic, progressive arthritis.

Animals↗
PubMed1989

Disparate functions of I-A and I-E molecules on B cells as evidenced by the inhibition with anti-I-A and anti-I-E antibodies of polyclonal B cell activation.

Polyclonal differentiation of unprimed B cells into IgM-producing cells induced by lipopolysaccharide (LPS) or T cell-derived lymphokine B151-TRF2 has been shown to contain a process of I-A-restricted B-B cell interaction, so that the B cell responses are inhibited by monoclonal antibodies (mAb) specific for I-A molecules. On the other hand, the B cell responses are also inhibited by anti-I-E mAb, although I-E molecules are not involved in such B-B cell interaction. In this study, we examined the mechanism underlying the anti-I-E-mediated inhibition of the B cell responses. The B cell responses induced by LPS or B151-TRF2 were inhibited by either anti-I-A or anti-I-E mAb added on day 0 over a 5-day culture period, whereas when added on day 3 the responses were inhibited only by anti-I-E mAb and not by anti-I-A mAb. To gain insight into the mechanism underlying the anti-I-E-mediated inhibition, we prepared monovalent Fab and divalent F(ab')2 fragments of anti-I-A and anti-I-E mAb and examined their effects on the B cell responses. We found that the B cell responses were inhibited by the F(ab')2 but not Fab fragment of anti-I-E mAb, whereas the Fab fragment of anti-I-A mAb still gave effective inhibition. The F(ab')2 but not Fab fragment of anti-I-E mAb induced increases in cyclic AMP (cAMP) levels in B cells, whereas the undigested anti-I-A mAb did not induce such increases. Furthermore, adenylate cyclase inhibitors, which inhibit cellular cAMP accumulation, circumvented the B cell responses inhibited by anti-I-E but not anti-I-A mAb. Thus, these results indicate that the anti-I-E-mediated inhibition of the B cell responses requires increases in intracellular cAMP levels induced by cross-linking of I-E molecules. In contrast, anti-I-A mAb inhibits the B cell responses without cross-linking of I-A molecules and cAMP accumulation. These results reinforce a unique function of I-A molecules as restriction elements in the Ia-restricted B-B cell interaction.

Animals↗
PubMed1989

Capacities of a newly established thymic stromal cell clone to express Ia antigens and to produce interleukin-6, colony-stimulating factor, and thymic stroma-derived T-cell growth factor.

Thymic stromal cell lines, termed MRL104 and MRL28, have been isolated from long-term liquid cultures of thymic stromal cells from MRL/l mice. The capacities of these parental lines and derived clones to express Ia antigens and to produce cytokines involved in T-cell proliferation and/or differentiation were investigated. Parental lines and their clones did not exhibit a typical fibroblastic, macrophage-like, or epithelial appearance in electron as well as phase-contrast micrographs. These thymic stromal cells seemed to differ from established fibroblast lines in that these thymic stromal cells expressed Ia antigens after exposure to interferon-gamma (IFN-gamma), whereas fibroblast lines did not. They also appeared to differ from macrophage cell lines in that they lacked the expression of Mac-1 antigens on their cell surface and produced no detectable level of interleukin-1 (IL1) before or even after exposure to lipopolysaccharide. When these parental lines and its clones were tested for their ability to produce various types of cytokines, it was revealed that they were capable of producing colony-stimulating factor (CSF), IL6, and thymic stroma-derived T cell growth factor (TSTGF), which was recently described, but were unable to generate other lymphokines and IFNs. Thus these cell lines and clones represent unique features in that they have potentials to express Ia antigens and to produce CSF, IL6, and TSTGF. The biological significance for the expression of these features is discussed in the context of intrathymic T-cell maturation and T-cell repertoire selection.

Animals↗
PubMed1989

Establishment of highly specific radioimmunoassays for neurokinin A and neurokinin B and determination of tissue distribution of these peptides in rat central nervous system.

Highly specific radioimmunoassays (RIAs) for neurokinin A (NKA) and neurokinin B (NKB) were developed. Antisera were produced by the procedure which involved immunization with NKA or NKB, both conjugated with keyhole limpet hemocyanin, and treatments with a tolerogenic conjugate of kassinin and a copolymer of D-glutamic acid and D-lysine (D-GL) to inhibit the production of cross-reactive antibodies against common C-terminal region of tachykinins. Cross-reactivities of anti-NKA antiserum (R704), thus produced, with NKB, kassinin, eledoisin were 12.6%, 10.6% and 11.5%, respectively. This was in sharp contrast with those of antiserum obtained from the rabbit not treated with kassinin-D-GL, these values corresponding to 129.0%, 42.5% and 94.4%, respectively. The cross-reactivities of R704 with substance P and physalaemin were 0.3% and 1.5%, respectively. This antiserum also bound 35.6% of neuropeptide K which contains NKA at its C-terminal. More importantly, anti-NKB antiserum (R707) obtained by the above tolerizing regimen was highly specific for NKB and the cross-reactivities with NKA, neuropeptide K, kassinin and other tachykinins were all less than 0.001%. RIAs using these specific antisera allowed us to measure directly NKA and NKB in tissue extracts without their fractionation by chromatography prior to RIAs. Measurements of immunoreactive NKA and NKB in different rat brain regions and spinal cord revealed that they are present with various ratios (NKA/NKB: 1.1-9.9) depending on the region.

Amino Acid Sequence↗
PubMed1989

Marked depression of brain cholecystokinin and vasoactive intestinal polypeptide levels in Eck fistula dogs.

Cholecystokinin-like immunoreactivity (CCK-LI) and vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) were measured in the brain of Eck fistula dogs and dimethylnitrosamine (DMN)-treated dogs which were prepared as experimental models of hepatic encephalopathy (HE). Significant reduction of CCK-LI was observed in all cortical regions of Eck fistula dogs, especially in parietal and occipital cortex (approximately 40% of control values). In DMN dogs, CCK-LI was reduced in the temporal, parietal and occipital cortex (65%, 47% and 51% of control values, respectively). Significant reduction of VIP-LI was also observed in the occipital cortex of both Eck fistula and DMN dogs (75% and 70% of control values, respectively). These data were compared with the concentrations of tyrosine and phenylalanine, precursors of false neurotransmitters suggested as causing HE. Phenylalanine was significantly increased in all areas of cortex of both models. Tyrosine was also significantly increased in frontal, parietal and occipital cortex of Eck fistula dogs, and in temporal, parietal and occipital cortex of DMN dogs. However, reduced amounts of these peptides did not correlate with increased amounts of the aromatic amino acids in these models. The results imply that reduced levels of CCK and VIP may be elicited by a mechanism distinct from that inducing increase of false neurotransmitters.

Amino Acids↗
PubMed1989

Lipopolysaccharide alteration mediated by the virulence plasmid of Salmonella.

Lipopolysaccharide (LPS) of Salmonella dublin, S. enteritidis, S. typhimurium, S. choleraesuis and their derivative strains was analysed to investigate the correlation between LPS and virulence plasmid of Salmonella. All wild-type strains had smooth type LPS, i.e. LPS with long O-specific polysaccharide. The virulence plasmid-cured strain of S. dublin, C524, exhibited a shorter O-specific chain than its parent strain, 5240. No distinct ladder bands were observed at the high molecular weight region on the SDS-PAGE gel for C524 LPS. By chemical analysis the number of O-repeating unit of C524 LPS was shown to be approximately one. The chain length of O-specific polysaccharide was restored by reintroduction of the virulence plasmid. The alteration of LPS by curing and reintroduction of the virulence plasmid was not observed when other wild-type strains of S. dublin were used. In the case of S. enteritidis, S. typhimurium, and S. choleraesuis, alteration of neither chemical composition nor electrophoretical profile of LPS was detected by curing and reintroduction of the virulence plasmids. Those results suggest that certain factor for regulation of the chain length of O-specific polysaccharide is encoded on the virulence plasmid of S. dublin.

Lipopolysaccharides↗
PubMed1989

Model for clonal elimination in the thymus.

A thymic stromal cell clone, MRL104.8a, expresses class I as well as class II H-2k antigens after exposure to gamma-interferon. This clone also produces thymic stroma-derived T-cell growth factor (TSTGF), which is distinct from other known interleukins and is capable of promoting the growth of various antigen-specific helper T cell (Th) clones without requiring a specific antigen or interleukin 2. When the keyhole limpet hemocyanin (KLH)-specific, I-Ek-restricted Th clone 9-16 was cultured on an Ia (I-Ak and I-Ek)-expressing MRL104.8a monolayer, potent proliferation of the 9-16 cells was induced by TSTGF produced by the monolayer. In contrast, the addition of KLH resulted in lethal growth inhibition of Th clone 9-16 cells. Another Th clone that is KLH-specific but I-Ab-restricted was capable of proliferating on the Iak-expressing MRL104.8a monolayer whether or not KLH was present. More importantly, death of Th clone 9-16 cells cultured on a MRL104.8a monolayer in the presence of KLH was almost completely prevented by the addition of anti-I-Ek or anti-CD3 monoclonal antibodies, which are capable of blocking antigen recognition by the T-cell receptor. However, when Th clone 9-16 cells were cultured in the presence of KLH but on a monolayer of MRL28.8a cells, another thymic stromal clone that expresses a comparable amount of I-Ek antigen but produces a marginal amount of TSTGF, cells did not die; a lethal effect was induced by adding TSTGF. These results indicate that the TSTGF-producing and Ia-expressing thymic stromal cells induce the continuous proliferation or selective elimination of each T-cell clone, depending on whether the T-cell receptor is stimulated by the relevant antigen associated with Ia molecules expressed on the stromal cell surface.

Animals↗
PubMed1989

Cluster formation among small resting B lymphocytes leading to B cell activation.

Intercellular contacts are thought to be a crucial event in various aspects of immune responses. We have recently suggested that the self class II MHC-restricted B-B cell interaction is a prerequisite process in the polyclonal B cell differentiation induced by a novel T cell-derived lymphokine B151-TRF2 or LPS. The results have led us to the possibility that such a class II MHC-restricted B-B cell interaction promotes the formation of B cell clusters responsible for the development of IgM-producing cells upon subsequent stimulation with the polyclonal B cell activator. To examine directly this possibility, the present study has utilized a recently devised ACAS470 work station capable of sorting out desired cells in a tissue culture plate in situ. Clusters and non-clusters were observed after 2 day preculture of murine resting B cells in the absence of the polyclonal B cell activator. Interestingly, B cells in clusters purified by the ACAS470 gave rise to IgM-producing cells when stimulated with B151-TRF2 or LPS for an additional 2 days, whereas non-clustered B cells failed to differentiate. Moreover, such a B cell activation was not observed when the 2 day preculture of the resting B cells was conducted in the presence of anti-class II MHC mAb but not of anti-class I MHC mAb. Thus, the present results support the notion that cluster formation among small resting B cells accompanying the class II MHC-restricted B-B cell interaction makes the B cells responsive to differentiation signals of polyclonal B cell activator.

Animals↗
PubMed1989

The tumor rejection antigen separated from Rous sarcoma virus-induced murine fibrosarcoma exhibits a molecular weight of approximately 60 kD but differs from functional pp60src.

The tumor antigen capable of inducing tumor resistance (tumor rejection antigen; TRA) was obtained in a solubilized form by sodium dodecyl sulfate (SDS) extraction of plasma membrane fraction from Rous sarcoma virus (RSV)-induced CSA1M fibrosarcoma cells (BALB/c origin). Analyses by Sephacryl S-300 gel filtration and SDS-polyacrylamide gel electrophoresis revealed that TRA activity was recovered in the fraction with a molecular weight of approximately 60 kD. Unfractionated crude SDS-solubilized preparation contained gp70 as detected by rabbit anti-gp70 antiserum, whereas such reactivity was lost in the fraction exhibiting the molecular weight of about 60 kD. Since this fraction retained pp60src activity, the relation of TRA to pp60src was further investigated. pp60v-src was also obtained from the lysate of v-src-expressing yeast transformant. Immunization of BALB/c mice with such pp60v-src-containing lysate failed to induce any significant tumor protection. The above 60 kD fraction of CSA1M solubilized antigens was allowed to bind to Sepharose beads coupled with anti-pp60src monoclonal antibody and separated into the bead-bound and bead-unbound fractions. The bead-bound fraction that was recovered from pp60src-binding beads (pp60src-positive fraction) did not exhibit the TRA activity. In contrast, immunization with the fraction depleted of pp60src activity (bead-unbound fraction) resulted in potent tumor protection. These results indicate that the solubilized membranous component(s) of CSA1M with a molecular weight of approximately 60 kD, which is distinct from functional pp60src, functions as the TRA against RSV-induced CSA1M tumor cells.

Animals↗
PubMed1989

[Biochemical characterization of tumor rejection antigen (TRA) and genetic control in anti-TRA immune responses].

A tumor antigen capable of inducing tumor resistance (tumor rejection antigen; TRA) was obtained in a solubilized form by sodium dodecyl sulfate (SDS)-extraction of plasma membrane fraction from Rous sarcoma virus (RSV)-induced CSA1M fibrosarcoma cells (BALB/c origin). Analyses by Sephacryl S-300 gel filtration and SDS-polyacrylamide gel electrophoresis revealed that TRA activity was recovered in the fraction of an approximate molecular weight (m. w.) of 60kD. Such TRA was also found to exist in plasma membrane fraction from various RSV-induced tumor cells but not from tumor cells induced with agents other than RSV. Unfractionated crude SDS-solubilized preparation contained gp 70 as detected by rabbit anti-gp 70 antiserum, whereas this reactivity was lost in the fraction exhibiting an m.w. of about 60 kD. Since this fraction retained pp60src activity, the relation of TRA to pp60src was further investigated. pp60src was also obtained from the lysate of v-src-expressing yeast transformant. Immunization of BALB/c mice with such pp60v-src-containing lysate failed to induce any significant tumor protection. The above 60 kD fraction of CSA1M solubilized antigens was allowed to bind to Sepharose beads coupled with anti-pp60src monoclonal antibody and was depleted of pp60src. Immunization with the fraction depleted of pp60src activity (bead-unbound fraction) resulted in potent tumor protection. These results indicate that the CSA1M solubilized membranous component(s) which has an approximate m.w. of 60kD but is (are) distinct from functional pp60src functions as the TRA against RSV-induced CSA1M tumor cells. The results are discussed in the context of (1) the relationship between the src gene and the expression of TRA and (2) genetic control in immune responses to the TRA common to RSV-induced tumor cells.

Animals↗
PubMed1989

[Analysis with immunoreactive CCKs and bioactive CCKs in rat duodenum and brain].

We extracted immunoreactive CCKs from rat duodenum and brain. We fractionated these samples by gel-filtration and analyzed with immunoreactivity and bioactivity of each fraction. 1) Elution profile of CCKs in duodenum and brain was well corresponding to that of bioactive CCKs. 2) Contents of CCKs determined by both RIA and Bioassay in each fraction were well correlated with each other. 3) Apparent molecular weights of CCKs of duodenum calibrated in column chromatography were approximately 2200, 1000 and 800. 4) Apparent molecular weight of CCK of brain seemed to be 1000.

Animals↗
PubMed1989

[Future perspectives on tumor-specific immunotherapy using hapten-reactive T cell activity].

Recent studies concerning cellular and molecular mechanisms of T cell-mediated immunity have revealed the involvement of various types of lymphokines. Irrespective of which types of lymphokines and cell-cell interactions among various T cell subsets are involved in the implementation of host immune responses against tumor, the feasible and practical approach is to use both molecular and cellular mechanisms for the augmented induction of effector T cell activity against tumor-resistant antigens (TRA). We have demonstrated previously that the in vivo effector T cells comprise 2 subsets of TRA-specific non-cytolytic CD4- and CD8-positive helper T cells, both of which release lymphokines and activate macrophages as an ultimate anti-tumor cytocidal effector. We have also defined conditions under which enhanced anti-tumor immunity can be obtained by pre-inducing potent helper T cell activity reactive to a certain antigenic determinant such as trinitrophenyl (TNP) residue of muramyl dipeptide (MDP)-derivatives as hapten, and immunized with tumor cells coupled with the corresponding haptenic determinant. This system induced most efficient and physiological cellular and molecular mechanisms responsible for the generation of tumor-specific effector T cell activity in vivo by virtue of the close linkage of hapten-reactive helper T cells and TRA-specific effector-precursor T cells in the microenvironment of hapten-coupled tumor cells. We have subsequently demonstrated that this protocol resulted in enhanced in vivo tumor protective immunity but also was applicable to the immunotherapy whereby a growing solid tumor as well as disseminated leukemia cells could be effectively eradicated in mice. Thus, these results emphasize the role of hapten-reactive helper T cell in augmenting tumor-specific immunity, and this protocol provides an effective maneuver for tumor-specific immunotherapy in human in future.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Property of class I H-2 alloantigen-reactive Lyt-2+ helper T cell subset. Abrogation of its proliferative and IL-2-producing capacities by intravenous injection of class I H-2-disparate allogeneic cells.

The present study investigates the distinctiveness of Class I H-2 alloantigen-reactive Lyt-2+ helper/proliferative T cell subset in the aspect of tolerance induction. Primary mixed lymphocyte reactions (MLR) revealed that Lyt-2+ and L3T4+ T cell subsets from C57BL/6 (B6) mice were exclusively capable of responding to class I H-2 [B6-C-H-2bm1 (bm1)]- and class II H-2 [B6-C-H-2bm12 (bm12)]-alloantigens, respectively. Anti-bm12 MLR was not affected by i.v. injection of bm12 spleen cells into recipient B6 mice. In contrast, a single i.v. administration of bm1 spleen cells into B6 mice resulted in the abrogation of the capacity of recipient B6 spleen and lymph node cells to give anti-bm1 MLR. This suppression was bm1 alloantigen-specific, since lymphoid cells from B6 mice i.v. presensitized with bm1 cells exhibited comparable anti-bm12 primary MLR to that obtained by normal B6 lymphoid cells. Such tolerance was rapidly (24 h after the i.v. injection of bm1 cells) inducible and lasting for at shortest 3 wk. Addition of lymphoid cells from anti-bm1-tolerant B6 mice to cultures of normal B6 lymphoid cells did not suppress the proliferative responses of the latter cells, indicating that the tolerance is not due to the induction of suppressor cells but attributed to the elimination or functional impairment of anti-bm1 proliferative clones. The tolerance was also demonstrated by the failure of tolerant lymphoid cells to produce IL-2. It was, however, found that anti-bm1 CTL responses were generated by tolerant lymphoid cells which were unable to induce the anti-bm1 MLR nor to produce detectable level of IL-2. These results demonstrate that class I H-2 alloantigen-reactive Lyt-2+ Th cell subset exhibits a distinct property which is expressed by neither Lyt-2+ CTL directed to class I H-2 nor L3T4+ Th cells to class II H-2 alloantigens.

Animals↗
PubMed1988

Autoimmune thyroiditis induced in mice depleted of particular T cell subsets. I. Requirement of Lyt-1 dull L3T4 bright normal T cells for the induction of thyroiditis.

T cell-depleted C3H/He or (C57BL/6xC3H/He)F1 (B6C3F1) mice were prepared by adult thymectomy and injection of antithymocyte serum, followed 3 wk later by lethal x-irradiation and bone marrow reconstitution. When these T cell-depleted mice were not injected or injected i.v. with normal spleen and lymph node cells treated with either anti-Thy-1, -L3T4 or -Lyt-2 antibody plus C or C alone, none of the groups of mice developed thyroiditis. In contrast, the adoptive transfer of normal cells treated with anti-Lyt-1 plus C resulted in high incidence of the production of antithyroglobulin antibody and the induction of typical thyroiditis lesion. The thyroid was the sole organ involved, because neither typical inflammatory lesion in other organs nor autoantibody such as anti-DNA antibody was detected in mice that exhibited thyroiditis. Analyses of surface phenotypes of cells required for inducing thyroiditis by the adoptive transfer revealed that an appreciable percentage of Lyt-1 dull T cells remained after the treatment of normal lymphoid cells with anti-Lyt-1 plus C. Almost all of these Lyt-1 dull T cells expressed magnitudes of L3T4 or Lyt-2 Ag comparable to those detected on Lyt-1 bright T cells. More important, the induction of thyroiditis was almost completely prevented by either in vitro or in vivo elimination of Lyt-1 dull L3T4+(bright) but not of Lyt-1 dull Lyt-2+(bright) T cells. These results indicate that Lyt-1 dull L3T4+ T cells existing in normal healthy individuals have potential to induce typical thyroiditis which is associated with the production of antithyroglobulin autoantibody, and that the activation and/or function of this T cell subset is regulated by the Lyt-1 bright T cell population coexisting in normal lymphoid cell population.

Animals↗