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H Braley-Mullen

Publications and source records attributed to H Braley-Mullen.

At least 37 records · Page 2Linked to original sources
PubMed1996

T cell receptor V beta usage in murine experimental autoimmune thyroiditis.

Mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg induced experimental autoimmune thyroiditis (EAT) in which the thyroid infiltrate consists primarily of mononuclear cells (MNC) (lymphocytic EAT). MTg-sensitized spleen cells cultured with MTg together with anti-IL2R antibody induce a granulomatous form of EAT in which the thyroid is infiltrated by MNC in addition to PMNs, histiocytes, and multinucleated giant cells. CD4+ T cells are the primary effector cells for both forms of EAT. The presence of specific T cell receptor (TCR) V beta families in the thyroid infiltrate was examined by flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR) amplification of mRNA. At the time of maximal disease severity, cells infiltrating the thyroid expressed primarily V beta 8, V beta 4, V beta 11, and V beta 14 as determined by flow cytometry. RT-PCR confirmed these findings and also detected several additional V beta gene families, including V beta 1, V beta 2, V beta 6, V beta 13, and V beta 15; V beta 3, V beta 10, and V beta 12 were also detected in some, but not all, experiments. There were no differences in the V beta T cell repertoires in thyroids of mice with lymphocytic vs granulomatous EAT. RT-PCR analysis of intrathyroidal MNC 11 days after cell transfer showed TCR V beta mRNA transcripts to be primarily restricted to V beta 4, V beta 11, and V beta 14, whereas the predominant thyroid-infiltrating T cell 21 days after cell transfer was V beta 8+. Depletion of V beta 8+ T cells in recipient mice did not reduce EAT severity. TCR V beta usage shifted predominantly to V beta 4+, V beta 11+, or V beta 14+ T cells of both CD4+ and CD8+ T cell subsets. These results indicate that multiple V beta TCR are expressed in thyroids of mice with EAT.

Animals↗
PubMed1996

The role of alpha 4 integrin and intercellular adhesion molecule-1 (ICAM-1) in murine experimental autoimmune thyroiditis.

Mouse-thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg induce a lymphocytic form of experimental autoimmune thyroiditis (EAT) whereas activation of the same cell population with MTg in the presence of anti-interleukin 2 receptor antibody (M7/20) induces a granulomatous form of EAT. The thyroid infiltrate in both lymphocytic and granulomatous EAT includes both CD4+ and CD8+ T cells and CD4+ T cells are the primary effector cells for both forms of EAT. This investigation was undertaken to begin to define the roles of alpha 4 integrin, and intercellular adhesion molecule-1 (ICAM-1) in the migration of CD4+ and CD8+ T cells to the thyroid in EAT. The studies presented here demonstrate the expression of alpha 4 integrin and ICAM-1 on CD4+ and CD8+ T cells infiltrating the thyroid and the expression of vascular cell adhesion molecule (VCAM) and ICAM-1 on thyroid cells of mice with EAT. The effects of anti-alpha 4 and anti-ICAM mAb administration on EAT severity in recipient mice was also determined. Anti-alpha 4 administration reduced or abolished lymphocyte infiltration in the thyroid resulting in reduced severity of both lymphocytic and granulomatous EAT. In contrast, anti-ICAM mAb had little effect on EAT severity. These results suggest that these two adhesion molecules exhibit differential functional roles in the modulation of EAT disease severity and that alpha 4-VCAM interactions may be of particular importance in trafficking of effector cells to the thyroid.

Animals↗
PubMed1995

Suppression of murine experimental autoimmune thyroiditis by oral administration of porcine thyroglobulin.

Experimental autoimmune thyroiditis (EAT) induced by the transfer of mouse thyroglobulin (MTg)-immunized spleen cells, activated in vitro with MTg, can be suppressed by oral administration of PTg to donor mice prior to immunization. Oral administration of 1 mg PTg five times over a 10-day period before immunization with MTg-LPS resulted in reduced EAT severity in recipient mice compared with recipients of cells from saline-fed immunized donors. MTg- or PTg-specific proliferative responses were not decreased in PTg-fed donors and anti-MTg antibody was not decreased in the donor mice fed 1 mg PTg. However, anti-MTg antibody production was markedly decreased in recipients of cells from PTg-fed donors compared with recipients of control cells. IgG1, IgG2A, and IgG2B anti-MTg antibody responses were all suppressed by PTg feeding suggesting that tolerance may be induced in both Th1 and Th2 cells. The more severe and histologically distinct granulomatous form of EAT was also suppressed by feeding PTg to donor mice. Studies are underway to determine the mechanism of oral tolerance in this model.

Administration, Oral↗
PubMed1995

Proliferation and autoantibody production by mouse thyroglobulin (MTg)-specific B cells activated in vitro by MTg and MTg-specific T cells.

Immunization of genetically susceptible strains of mice with mouse thyroglobulin (MTg) and adjuvant results in sensitization of MTg-specific CD4+ T cells that can induce experimental autoimmune thyroiditis (EAT) after in vitro activation with MTg. These MTg specific CD4+ T cells also provide help to MTg-specific B cells which produce anti-MTg autoantibodies in vivo. This study was undertaken to develop a system with which to measure MTg-specific helper function in vitro. MTg-activated T cells were shown to provide help to MTg-primed B cells in vitro as assessed by B-cell proliferation and anti-MTg autoantibody production. These responses were MTg-specific and required MTg priming of both the T- and B-cell populations. An MTg-specific CD4+ T-cell line also induced MTg-specific B-cell proliferation and was capable of inducing IgG1, IgG2a and IgG2b synthesis in MTg- primed B cells.

Animals↗
PubMed1994

Differential requirement for autoantibody-producing B cells for induction of lymphocytic versus granulomatous experimental autoimmune thyroiditis.

Mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTG transfer experimental autoimmune thyroiditis (EAT) in which the thyroid cellular infiltrate consists primarily of mononuclear cells (lymphocytic EAT). Addition of anti-IL2R antibody to cultures with MTg leads to activation of cells that induce granulomatous EAT, accompanied by high serum anti-MTg autoantibody responses, in recipient mice. CD4+ T cells are required to induce both forms of EAT; whether B cells and/or autoantibodies produced by MTg-sensitized B cells also contribute to disease severity or the type of thyroid histopathology is unknown. In our study, B cells and autoantibody responses produced in recipient mice were reduced either by column removal of B cells from donor spleen cells or by treatment of recipient mice with anti-I-AK mAb at the time of cell transfer. These maneuvers only slightly reduced the severity of lymphocytic EAT but markedly reduced the severity and incidence of granulomatous EAT developing in recipient mice. Delaying the initiation of anti-I-AK treatment until 6 days after cell transfer was less effective in reducing anti-MTg autoantibody responses or granulomatous EAT. These studies all suggested that anti-MTg autoantibodies were required for development of granulomatous but not lymphocytic EAT. However anti-I-AK-treated recipients receiving injections of anti-MTg antibody or having serum antibody induced by prior immunization with MTg and LPS also developed less severe granulomatous EAT than controls. These results suggest that sensitized CD4+ T cells and circulating anti-MTg autoantibody are not sufficient for development of granulomatous thyroid lesions. It is possible that antibodies having a unique function or specificity are produced in mice developing granulomatous EAT or thyroid-infiltrating B cells may directly contribute to the granulomatous inflammatory response.

Animals↗
PubMed1994

Regulation of the induction and resolution of granulomatous experimental autoimmune thyroiditis in mice by CD8+ T cells.

Mouse thyroglobulin (MTg)--sensitized spleen cells activated in vitro with MTg induce experimental autoimmune thyroiditis (EAT) in which the thyroid cellular infiltrate consists primarily of mononuclear cells (lymphocytic EAT). Cells cultured with MTg plus anti-IL2R antibody induce EAT having a granulomatous histopathology. CD4+ T cells are required to induce both forms of EAT. The potential contribution of CD8+ T cells in the pathology of lymphocytic vs granulomatous EAT was addressed using anti-CD8 mAb to deplete CD8+ T cells from donor or recipient mice. Depletion of donor CD8+ T cells had little effect on EAT severity induced by cells cultured with MTg or MTg plus anti-IL2R mAb. However, recipients of CD8-depleted cells activated with MTg induced granulomatous EAT whereas cells from untreated donors activated with MTg alone induced lymphocytic EAT. Similar results were obtained when anti-CD8 mAb was added to cultures to block activation of CD8+ T cells. Injection of anti-CD8 mAb into recipient mice slightly increased the severity of EAT induced by cells cultured with MTg or MTg and anti-IL2R mAb when EAT was assessed 19-20 days after cell transfer. Cells cultured with MTg alone induced mild granulomatous EAT in most anti-CD8-treated recipients. When thyroids of mice which had granulomatous EAT on Day 19 were examined 47 or 60 days after cell transfer, the granulomatous inflammatory response in untreated recipients had almost completely resolved. In contrast, granulomatous EAT persisted and often became more severe in anti-CD8-treated recipients. Anti-CD8 treatment did not influence lymphocytic EAT assessed late after cell transfer. These results indicate that CD8+ T cells are required for the resolution of granulomatous EAT.

Animals↗
PubMed1994

Requirement for B cell-derived immunoglobulin for Th activation by the type 2 antigen polyvinylpyrrolidone.

Th specific for the type 2 antigen polyvinylpyrrolidone (PVP) could not be activated in vivo or in vitro in mice rendered B cell deficient by treatment from birth with anti-IgM. The requirement for B cells was apparently not due to a requirement for B cells to function as antigen presenting cells for Th activation since T cells also were not activated when anti-IgM treated mice were reconstituted with B cells prior to priming with PVP. In addition, removal of B cells from spleens of adult of adult mice had no effect on the ability of PVP to activate Th in vitro. Potential non-specific effects of chronic anti-IgM treatment on T cell function are unlikely since T cells from anti-IgM treated mice provided help to B cells for antibody responses to horse red blood cells responded normally to T cell mitogens and had a CD4:CD8 ratio like that of untreated mice; PVP primed T cells from anti-IgM treated mice also did not actively suppress the helper activity of PVP primed T cells from normal mice. In addition, PVP-specific Th were able to be activated in mice given multiple injections of anti-IgM beginning 2 weeks after birth and in mice given MOPC 104E IgM together with anti-IgM; under these conditions B cell depletion by the anti-IgM did not occur. Thus activation of PVP-specific Th requires that B cells be present during the first few weeks after birth. Experiments in which mice were given injections of normal mice Ig together with the anti-IgM indicate that the function of B cells for Th activation in this system can be replaced by B cell-derived Ig. Thus PVP-specific Th could be activated in mice treated from birth with anti-IgM plus normal Ig despite the absence of significant numbers of B cells in the spleens of these mice.

Animals↗
PubMed1994

Intrathyroidal cell phenotype in murine lymphocytic and granulomatous experimental autoimmune thyroiditis.

In-vitro mouse thyroglobulin (MTg) activated spleen cells from immunized donor mice can induce experimental autoimmune thyroiditis (EAT) after transfer to recipient mice. The intrathyroidal cellular infiltrate consists primarily of mononuclear cells (lymphocytic EAT). Cells cultured with MTg together with anti-IL2R antibody induce EAT with a granulomatous histopathology in which the thyroid infiltrate contains mononuclear cells (MNC) in addition to PMN's histiocytes, and multinucleated giant cells. Flow cytometric analysis of intrathyroidal MNC infiltrates demonstrated that both CD4+ and CD8+ T cells infiltrate the thyroid in both lymphocytic and granulomatous EAT and that CD8+ T cells outnumber CD4+ T cells. There were usually increased numbers of PMN's in the granulomatous thyroids, but low number of Ig+ and F4/80+ cells (macrophages) in the intrathyroidal infiltrate of both disease types. IL2R and Pgp-1 were expressed on both CD4+ and CD8+ intrathyroidal T cells. The majority of CD8+ cells were ICAM+, LFA-1+, and CD45RB+ whereas only a small percentage of CD4+ intrathyroidal T cells expressed these markers. There were no major differences in intrathyroidal MNC phenotype between lymphocytic and granulomatous EAT. Depletion of CD8+ T cells in recipient mice did not reduce EAT severity and resulted in an increased percentage of intrathyroidal CD4+ T cells expressing IL2R. These results suggest that CD8+ T cells are not functioning as effector cells in lymphocytic or granulomatous EAT.

Animals↗
PubMed1992

Induction of granulomatous experimental autoimmune thyroiditis in mice with in vitro activated effector T cells and anti-IFN-gamma antibody.

Experimental autoimmune thyroiditis (EAT) can be induced in mice after the transfer of mouse thyroglobulin (MTg)-sensitized donor spleen cells that have been activated in vitro with MTg. CD4+ T cells are required for the transfer of EAT in this model. Because CD4+ T cells produce various lymphokines, such as IFN-gamma, that may be involved in the activation or regulation of the immune response to MTg and the development of EAT, the present study was undertaken to determine whether a neutralizing mAb to IFN-gamma could modulate the induction or expression of EAT. The anti-IFN-gamma mAb XMG-1.2 had no effect on sensitization of donor cells. However, addition of XMG-1.2 mAb during in vitro activation of MTg-primed spleen cells resulted in more severe EAT in recipient mice. The thyroid lesions in recipients of cells cultured with MTg and XMG-1.2 mAb also exhibited granulomatous changes, which differed qualitatively from the predominantly lymphocytic cell infiltrates in recipients of cells cultured with MTg alone. Recipients of MTg-activated spleen cells also developed severe granulomatous EAT when they were given injections of XMG-1.2 mAb. The effects of XMG-1.2 could be neutralized by IFN-gamma. Recipients of cells cultured in the presence of XMG-1.2 mAb had augmented autoantibody responses, although there were no apparent differences in the IgG subclass distribution of the anti-MTg autoantibody responses. These studies suggest that neutralization of endogenous IFN-gamma results in increased activity of cells capable of inducing granulomatous EAT in mice.

Animals↗
PubMed1991

Induction of severe granulomatous experimental autoimmune thyroiditis in mice by effector cells activated in the presence of anti-interleukin 2 receptor antibody.

Spleen cells from CBA/J mice immunized with mouse thyroglobulin (MTg) and the adjuvant lipopolysaccharide induce experimental autoimmune thyroiditis (EAT) after transfer to recipient mice if they are first activated in vitro with MTg. EAT induced by cells cultured with MTg is generally moderate in severity and is characterized by a thyroid infiltration consisting primarily of mononuclear cells. Addition of the anti-interleukin 2 receptor (IL-2R) monoclonal antibodies (mAbs) M7/20, 3C7, or 7D4 to spleen cell cultures with MTg resulted in a cell population capable of inducing a more severe type of EAT characterized by extensive follicular destruction, granuloma formation, and the presence of multinucleated giant cells. Recipients of cells cultured with MTg and anti-IL-2R mAb also had higher anti-MTg autoantibody responses than recipients of cells cultured with MTg alone. Activation of cells capable of transferring severe granulomatous EAT and increased anti-MTg autoantibody responses required both MTg and M7/20 in culture and required addition of M7/20 within the first 8 h of the 72-h culture period. CD4+ T cells were required for the expression of both the severe granulomatous EAT lesions and the mononuclear cell infiltrates typically observed in murine EAT. The increased anti-MTg autoantibody responses in recipients of cells cultured with MTg and anti-IL-2R mAbs were not restricted to a particular immunoglobulin G (IgG) subclass and included antibody of the IgG1, IgG2A, and IgG2B subclasses. These results suggest that a subset of CD4+ T cells capable of inducing severe granulomatous EAT and increased anti-MTg autoantibody responses is preferentially activated when cells are cultured in the presence of anti-IL-2R mAb. Anti-IL-2R mAb may either prevent activation of cells that induce classical lymphocytic EAT or prevent activation of cells that normally function to downregulate EAT effector T cell activity.

Animals↗
PubMed1990

Requirement for B cells for activation of contrasuppressor T cells by type III pneumococcal polysaccharide.

Type III pneumococcal polysaccharide (S3) is unable to activate S3-specific contrasuppressor T cells (Tcs) in mice depleted of B cells by chronic anti-IgM treatment or in immune defective xid mice that lack the B cell subset required for anti-S3 antibody responses. The inability of S3 to activate Tcs in xid mice was shown to be due to a requirement of B cells for Tcs activation rather than to an absence of Tcs in xid mice. The B cells from normal mice that are required for Tcs activation apparently function to present the S3 Ag to Tcs. S3 physically coupled to spleen cells (S3-SC) prepared from normal BCF1 SC could activate Tcs in both xid and BCF1 mice whereas S3-SC prepared from xid SC or B cell-depleted BCF1 SC could not activate Tcs in either strain. B cell APC function was abrogated by 3000 R irradiation and by treatment of the B cells with either chloroquine or paraformaldehyde. Interestingly, B cells from mice previously immunized with S3 were unable to function in Tcs activation; preimmunization of B cell donors with an irrelevant Ag or with a T-dependent form of S3 had no effect on their ability to function as APC. These latter observations are discussed in terms of the in vivo persistence of polysaccharide Ag and their ability to induce B cell tolerance under the experimental conditions used for these experiments. The results of this study provide evidence that B cells play an important and apparently obligatory role in the activation of Tcs by S3; B cells apparently function to present Ag to Tcs, resulting in the activation of this regulatory T cell subset.

Animals↗
PubMed1990

Type 6 and 19 pneumococcal polysaccharides coupled to erythrocytes elicit pneumococcal cell wall-specific primary IgM responses and capsular polysaccharide-specific secondary IgG responses.

Previous results have shown that the primary murine antibody responses to vaccine preparations of type 6 (S6; Danish type 6A) or type 19 (S19; Danish type 19F) pneumococcal capsular polysaccharides consist entirely of IgM antipneumococcal cell wall carbohydrate (PnC)-specific antibodies. No capsular polysaccharide-specific IgM antibodies were detectable by plaque-forming cell or enzyme-linked immunosorbent assay techniques. In this report, antibodies specific for S6 and S19 capsular polysaccharides were induced in secondary responses to chicken erythrocyte (CRBC) conjugates of S6 and S19. Essentially all detectable IgG produced in the secondary response was capsular polysaccharide specific and included all subclasses of IgG. In contrast, all detectable IgM produced in the primary response to S6-CRBC and S19-CRBC, and the IgM produced in the secondary response to S6-CRBC was not capsular polysaccharide specific since it reacted with PnC. Thus, there is a major change in the specificity of the primary IgM response compared to the secondary IgG response of mice immunized with S6-CRBC or S19-CRBC. Injection of PnC or any PnC-containing polysaccharide prior to immunization with S6-CRBC or S19-CRBC resulted in suppression of the primary IgM response. In contrast, only the capsular polysaccharide used in the immunizing polysaccharide-erythrocyte conjugate suppressed induction of the capsular polysaccharide-specific secondary IgG response. These results suggest that S6 and S19 capsular polysaccharide-specific IgG-producing memory B cells derive from capsular polysaccharide-specific precursors which do not produce detectable antibody after primary immunization.

Animals↗
PubMed1990

Distinct populations of antigen-presenting cells are required for activation of suppressor and contrasuppressor T cells by type III pneumococcal polysaccharide.

Type III pneumococcal polysaccharide (S3) coupled to spleen cells (S3-SC) has been shown to activate S3-specific Ts and Tcs in mice. Ts activation required I-J identity between carrier SC and Ts donors whereas I-A identity was required for Tcs activation. The carrier SC therefore presumably function as APC for Ts and Tcs activation by S3 since they are apparently not represented by APC present in the Ts and Tcs donors. The properties of the APC required for activation of S3-specific Ts and Tcs were determined by coupling S3 to various spleen cell subpopulations and assessing the ability of the various S3-SC populations to activate Ts and Tcs. The results indicate that Ts and Tcs are preferentially activated when S3 is presented on distinct cell types. S3-specific Ts were activated when S3 was coupled to plastic adherent cells. These cells are nonadherent to anti-Ig and nonfunctional in cyclophosphamide (Cy)-treated mice and their function is eliminated following treatment of cells with either anti-I-A or anti-I-J and C. In contrast, S3-specific Tcs were activated when S3 was coupled to anti-Ig adherent SC which bear I-A and the B cell marker J11d. These cells are functional in Cy-treated mice and their function is resistant to treatment with anti-I-J and C. Thus presentation of S3 on distinct cell types results in the preferential activation of T cells having opposing immunoregulatory function.

Animals↗
PubMed1990

Effects of anti-I-A and anti-I-E monoclonal antibodies on the induction and expression of experimental autoimmune thyroiditis in mice.

Susceptibility to experimental autoimmune thyroiditis (EAT) in mice is linked to the I-A subregion of the major histocompatibility complex (MHC). The present study was undertaken to assess the effectiveness of anti-I-Ak monoclonal antibody (MAb) 10-2.16 in preventing or arresting the development of EAT. Spleen cells from CBA/J or (CBA/J x Balb/c) F1 mice given 10-2.16 prior to sensitization with mouse thyroglobulin (MTg) and adjuvant could not transfer EAT to normal recipients, and cells from these mice did not proliferate in vitro to MTg. Donor CBA/J mice given 10-2.16 before immunization and recipients of cells from such mice produced little MTg-specific IgG1 or IgG2b antibody but did produce nearly as much IgG2a as controls. The effects of in vivo treatment with 10-2.16 appear to be due to elimination of Ia + cells rather than to modulation of Ia or induction of suppressor T cells. When 10-2.16 was added to in vitro cultures it also prevented the proliferation and activation of sensitized CBA/J or F1 effector cell precursors. Other mAb specific for MHC class II gene products, but not associated with disease susceptibility, expressed by CBA/J (I-Ek) or F1 (I-Ad) mice (14-4-4S or MK-D6 respectively), also prevented in vivo sensitization, but did not block in vitro activation. Anti-I-Ak was also effective in preventing EAT if multiple injections of mAb were given to recipients of sensitized EAT effector cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Regulation of IgG responses by helper and suppressor T cells activated by pneumococcal capsular polysaccharides.

Type 2 antigens are usually unable to prime the helper T cells (TH) required for secondary IgG antibody responses. However, previous results from this laboratory indicated that low doses of the type 2 antigen polyvinylpyrrolidone (PVP) could activate T cells which provided help to PVP-primed B cells for the production of PVP-specific IgG antibody. Therefore, it was of interest to determine if other type 2 antigens may also be able to activate TH. Low doses of S19 or S3 (subimmunogenic for a primary IgM response) activated TH capable of providing help to S19- or S3-CRBC-primed B cells for a secondary IgG response. Higher doses of these antigens (optimally immunogenic for a primary IgM response) activated suppressor T cells (TS). Removal of these TS prior to transfer of T cells to recipient mice resulted in expression of TH function. Therefore, the preferential activation of TH versus TS was dependent on the dose of antigen used for priming. TH activated by low doses of S19 expressed Thy 1 and L3T4 and were antigen specific. In contrast to the ability of low doses of PVP to prime B cells for secondary IgG responses, low doses of S3 and S19 did not prime capsular polysaccharide-specific IgG memory B cells. High doses of S3 were able to prime B cells if TS precursors were first removed by treatment of mice with cyclophosphamide (Cy), whereas high doses of S19 did not prime B cells for secondary IgG responses in either Cy-treated or control mice. These results are discussed in relation to the general observations that type 2 antigens may not activate antigen-specific TH.

Animals↗
PubMed1989

Production and characterization of monoclonal antibodies specific for types 6 and 19 pneumococcal capsular polysaccharides.

The primary IgM and the secondary IgG antibody responses to pneumococcal capsular polysaccharides type 19 (S19) and type 6 (S6) coupled to sheep erythrocytes (S19-SRBC or S6-SRBC) differ in specificity. Although the primary IgM response appears to be totally specific for the pneumococcal cell wall carbohydrate (PnC) which is present in these polysaccharide preparations, the secondary IgG response appears to be completely specific for the immunizing capsular polysaccharide. A library of B cell hybridomas from fusions of splenocytes undergoing a primary response to an S19 preparation consisted entirely of PnC-specific hybrids. Thus, no evidence was obtained for the presence of capsular polysaccharide-specific IgM secreting B cells. IgM and IgG antibody secreting hybridomas were obtained, from fusions of splenocytes undergoing secondary S6- or S19-SRBC responses, to examine the antigen specificity of secondary antibody response of B cells at the clonal level. Many of the secondary IgM hybridomas secreted PnC-specific antibody; however, several S6-specific IgM secreting hybrids were also obtained, demonstrating a previously undetected population of B cells. All IgG secreting hybridomas obtained from S19- or S6-SRBC secondary response fusions secreted capsular polysaccharide-specific antibody, thus confirming the apparent absence of PnC-specific IgG secreting B cells in these responses. This method of immunization and challenge of mice with capsular polysaccharide coupled to erythrocytes, which results in the production of capsular polysaccharide-specific IgG responses, offers a relatively straightforward means to generate monoclonal antibodies specific for pneumococcal capsular polysaccharides.

Animals↗
PubMed1988

Prevention and reversal of experimental autoimmune thyroiditis (EAT) in mice by administration of anti-L3T4 monoclonal antibody at different stages of disease development.

Experimental autoimmune thyroiditis (EAT) can be induced in CBA/J mice following the transfer of spleen cells from mouse thyroglobulin (MTg)-sensitized donors that have been activated in vitro with MTg. Since L3T4+ T cells are required to transfer EAT in this model, the present study was undertaken to assess the effectiveness of the anti-L3T4 monoclonal antibody (mAb) GK1.5 in preventing or arresting the development of EAT. Spleen cells from mice given mAb GK1.5 prior to sensitization with MTg and adjuvant could not transfer EAT to normal recipients and cells from these mice did not proliferate in vitro to MTg. Donor mice given GK1.5 before immunization did not develop anti-MTg autoantibody and recipients of cells from such mice also produced little anti-MTg. GK1.5 could also prevent the proliferation and activation of sensitized effector cell precursors when added to in vitro cultures. When a single injection of mAb GK1.5 was given to recipients of in vitro-activated spleen cells, EAT was reduced whether the mAb was given prior to cell transfer or as late as 19 days after cell transfer. Whereas the incidence and severity of EAT was consistently reduced by injecting recipient mice with GK1.5, the same mice generally had no reduction in anti-MTg autoantibody. Since EAT is consistently induced in control recipients by 14-19 days after cell transfer, the ability of mAb GK1.5 to inhibit EAT when injected 14 or 19 days after cell transfer indicates that a single injection of the mAb GK1.5 can cause reversal of the histopathologic lesions of EAT in mice. These studies further establish the important role of L3T4+ T cells in the pathogenesis of EAT in mice and also suggest that therapy with an appropriate mAb may be an effective treatment for certain autoimmune diseases even when the therapy is initiated late in the course of the disease.

Animals↗