Effects of in vivo T-cell depletion on immunity to Eimeria falciformis.
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Biomedical subjects
K T HayGlass
Publications and source records attributed to K T HayGlass.
The role of B cells for in vivo T cell responses to a Friend virus-induced leukemia.
B cells can function as antigen-presenting cells and accessory cells for T cell responses. This study evaluated the role of B cells in the induction of protective T cell immunity to a Friend murine leukemia virus (F-MuLV)-induced leukemia (FBL). B cell-deficient mice exhibited significantly reduced tumor-specific CD4+ helper and CD8+ cytotoxic T cell responses after priming with FBL or a recombinant vaccinia virus containing F-MuLV antigens. Moreover, these mice had diminished T cell responses to the vaccinia viral antigens. Tumor-primed T cells transferred into B cell-deficient mice effectively eradicated disseminated FBL. Thus, B cells appear necessary for efficient priming but not expression of tumor and viral T cell immunity.
Animals↗
Isotype-selective abrogation of established IgE responses.
Chemically modified allergens have been extensively studied in an attempt to develop materials of increased efficacy and improved safety for use in the immunotherapy of allergic disease. Most of the strategies that have been developed yield products that strongly inhibit de novo IgE responses but have only marginal impact on ongoing IgE responses. We report the virtual abrogation of pre-established murine anti-ovalbumin IgE responses using a glutaraldehyde-polymerized ovalbumin preparation (OA-POL) of Mr 3.5 x 10(7). Secondary IgE responses are inhibited by 97-99% over a period of at least 8 months following three i.p. courses of OA-POL treatment. Administration of five additional ovalbumin [Al(OH)3] booster immunizations over this period fails to alter this unresponsive state. The inhibition of antigen-specific IgE responses is isotype specific.
Animals↗
Antigen- and isotype-specific regulation of IgE responses by Lyt 1+,2,3- and Lyt 1-,2,3+ T suppressor cells.
Antigen-specific, IgE isotype-selective suppression is induced following treatment of mice with a high-molecular-weight glutaraldehyde-polymerized ovalbumin preparation (OA-POL). The results show that the suppression is mediated by Lyt 1+,2,3- cells residing in the spleen. Adoptive transfer experiments indicate that Lyt 2,3+ or Lyt 1,2,3+ cells are not required for the establishment of suppression by these Lyt 1+,2,3- suppressor T cells (Ts). Treatment of OA-POL-induced Ts cells with anti-I-Jk serum and complement does not affect their ability to suppress. In marked contrast, spleen cells from animals treated with a single course of OA-POL almost 300 days previously, were shown to contain boosterable memory suppressor T cells (Tsm) which display the Lyt 1-,2,3+ phenotype. The activity of both Ts and Tsm cells appears to result from stimulation by determinants common to native OA and OA-POL rather than by idiotypic determinants expressed on anti-OA antibodies.
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Suppressor T-cell factor(s) display an altered pattern of Igh (immunoglobulin heavy chain locus) genetic restriction when developed in an Igh-congeneic host.
Suppressor T-cell factor(s) (TsF1) inhibit the in vivo priming of azobenzenearsonate-specific cytotoxic T-cell responses. The activity of TsF1 is restricted by genes linked to Igh-1 allotypic markers. TsF1 obtained from B6.Igh-1n mice was unable to suppress the immune response in B6.Igh-1b mice and vice versa. However, TsF1 prepared from B6.Igh-1n T cells "parked" in an Igh-congeneic B6.Igh-1b environment displays an additional restriction specificity of the host. Thus, TsF1 prepared from these Igh-chimeric mice suppressed immune responses in both B6.Igh-1n (donor) and B6.Igh-1b (recipient) mice but not in mice of the unrelated strain BALB/c.Igh-1a. The results indicate that the establishment of the suppressor T-cell repertoire is dependent not only upon the genetic background of the individual T cell but also upon the influence of Igh-linked determinants present when T-cell clones are selected during the response.
Animals↗
T cell development in B cell deficient mice. III. Restriction specificity of suppressor T cell factor(s) produced in mice treated chronically with rabbit anti-mouse mu chain antibody.
A role for Igh linked genes and the idiotypes they encode has been implicated in the activity of a variety of T cell subpopulations. Idiotype restricted T cell function has been observed for helper and suppressor cell populations. The finding that T cell receptor genes are distinct from B cell receptor (Igh) genes strongly argues against a direct role for immunoglobulin genes in the determination of the T cell repertoire. Nevertheless, idiotypic Ig determinants may play an indirect role in influencing the ultimate composition of the T cell repertoire. One approach to this question involves evaluation of T cell activity upon development in an immunoglobulin deficient environment. The availability of antigens which elicit T cell and antibody responses characterized by the expression of dominant crossreactive idiotypes under the control of Igh genes provides an ideal approach to investigate the basis for the expression of Igh-like structures on T cells and the concomitant functional genetic restrictions they determine. Thus, we have prepared B cell deficient mice by continuous treatment, beginning at birth, with rabbit anti-mouse IgM. The network which comprises the suppressor T cell response to azobenzenearsonate (ABA) was then examined in normal and anti-mu treated mice to assess what role, if any, immunoglobulin encoded determinants play in influencing the composition of the peripheral T cell pool. The results clearly demonstrate that the absence of Ig+ B cells leads to major alterations in the composition of the T cell repertoire. Anti-mu treated, but not normal rabbit Ig treated, mice produce TsF1 which fails to suppress cytotoxic T lymphocyte or helper T cell responses of normal syngeneic mice, yet efficiently suppresses those of syngeneic anti-mu treated recipients. Reciprocally, normal TsF1, though suppressive in normal Igh-1 syngeneic recipients, fails to affect the development of responses in anti-mu treated syngeneic mice. TsF1 obtained from anti-mu treated mice is antigen-specific. Testing of anti-mu TsF in a variety of normal or anti-mu treated recipients reveals no MHC restrictions. In marked contrast, anti-mu TsF reflects a novel pattern of Igh functional restrictions. The observed Igh restrictions were found to map to the idiotype encoding VH regions of the Ig heavy chain gene cluster (Igh-VH). The results demonstrate that T cell maturation in the virtual absence of environmental immunoglobulin can lead to profound changes in the composition of the T cell compartment. The means by which the absence of Ig encoded determinants leads to such changes is speculated upon.
Agammaglobulinemia↗
Suppression of the IgE antibody response by glutaraldehyde-modified ovalbumin: dissociation between loss of antigenic reactivity and ability to induce suppression.
Ovalbumin (OA) was substituted with glutaraldehyde (GA) at various GA:OA ratios and several preparations were isolated by gel filtration according to molecular weight. Two GA-substituted but unpolymerized preparations (OA1-L and OA1-H) and 3 polymerized preparations of increasing molecular weight (OA4, OA175 and OA-POL) were obtained and were assessed for their ability to react with IgG and IgE antibodies directed against the native OA molecule, as well as for their ability to suppress the IgE antibody response. The results show that while both polymerized and unpolymerized GA-modified preparations lost their reactivity towards antinative OA antibodies, to a considerable extent, their ability to suppress the OA/IgE antibody response was directly dependent on polymerization. Pretreatment of CBA mice with unpolymerized OA preparations was ineffective while the effect of pretreatment with three polymers (OA4, OA175 and OA-POL) was directly dependent on the size of the polymer. The ability to induce IgG antibodies or delayed hypersensitivity to OA was not suppressed.
Aldehydes↗
Demonstration of long-lived memory T suppressor cells in the IgE response.
Administration to mice of repeated small doses of glutaraldehyde-polymerized ovalbumin (OA-POL) results in drastic suppression of the IgE antibody response. The high anamnestic IgE antibody responses usually obtained after 2 injections of native OA in alum were completely abrogated when OA-POL was administered between the 2 immunizations. Treatment with OA-POL prior to a primary immunization with 2 micrograms DNP-OA in alum induced a profound suppression of both anti-DNP and anticarrier IgE responses. The suppression, which was detectable for at least 7 months, was antigen-specific, selective for the IgE class and was sensitive to treatment of spleen cells with anti-Thy-1.2 antibody and complement. Adoptive transfer of spleen cells from donors treated with OA-POL 200 days, 16 days or 200 and 16 days prior to transfer, resulted in different kinetics of suppression in the recipient. The results are consistent with the presence of long-lived IgE-selective T suppressor cell memory. The possibility that separate Ts and Ts memory cell populations are generated is discussed.
Animals↗
Antigen- and IgE class-specific suppression mediated by T suppressor cells of mice treated with glutaraldehyde-polymerized ovalbumin.
Various size polymers are obtained following glutaraldehyde treatment of native ovalbumin (OA). OA-POL, approximately 35 X 10(6) daltons, was prepared at the isoelectric point of OA. Treatment of CBA mice with microgram amounts of OA-POL led to efficient antigen-specific suppression of IgE responses. IgG anti-OA antibodies were not suppressed. Transfer of cells from OA-POL-treated donors into normal, unprimed recipients interfered with the ability of these animals to mount a primary or secondary IgE response. In addition, cotransfer of spleen cells from OA-POL-treated mice along with OA (in alum)-primed cells, into irradiated syngeneic recipients resulted in IgE class-specific suppression that was abrogated by treatment of OA-POL donor cells with monoclonal anti-Thy 1.2 + complement. The presence or absence of T cells in the OA-POL population had no effect on IgG levels in the recipients. Analysis of the antigenic properties of OA-POL revealed 5-15% cross-reactivity with native OA as perceived by IgG or IgE antibodies. In contrast, OA-POL was highly cross-reactive at the T cell level as shown functionally by its potent induction of OA-specific, IgE-selective suppressor T cells. The results suggest that the beneficial effects of glutaraldehyde-modified allergens, recently introduced in the immunotherapy of atopic individuals may be due to the preferential exposure on the polymerized protein, of antigenic determinants generating T suppressor cells and to the selective loss of B cell-reactive determinants.
Animals↗
IP-10 mediated reinforcement of human type 1 cytokine synthesis to environmental allergens among non-atopic subjects.
BACKGROUND: Non-atopic subjects do not differ from those with allergic rhinitis or asthma in their ability to respond to environmental antigens, but in the nature of their response. IP-10, a CXC (alpha) chemokine, is produced by a wide variety of cell types, and differs from most chemokines in its specificity for activated lymphocytes. Here, we examine its potential role in the maintenance of putatively protective, type-1-dominated cytokine responses among non-atopic individuals. METHODS: The impact of rIP-10 on polyclonally driven, grass-pollen-and cat-antigen-stimulated type 1 (IFNgamma) and type 2 (IL-4) cytokine responses was examined in short-term cultures of fresh PBMC from non-atopic subjects directly ex vivo. RESULTS: rIP-10 selectively enhanced polyclonally driven and antigen-specific IFNgamma, but not IL-4, responses, with median increases ranging from 100 to 400% following polyclonal activation and 20 to 30-fold in antigen-driven IFNgamma responses. rIP-10 levels with maximal activity were at or below those previously reported for maximal chemotactic activity and, most importantly, were within the range of those seen in plasma obtained from non-atopic subjects during the grass pollen season. CONCLUSIONS: The data suggest a potential role for IP-10 in the maintenance of protective, type-1-dominated responses in non-atopic subjects. They raise the possibility that this chemokine could be of therapeutic value in individuals with established type-2-dominated responses, e. g. in patients with immediate hypersensitivity.
Allergens↗
Exogenous IL-12 and directed induction of human and murine Th1-associated responses.
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