Properties of antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. I. In vivo activity and immunochemical characterization.

Takemori, Toshitada; Tada, Tomio

doi:10.1084/jem.142.5.1241

Cited by 170 publications

(75 citation statements)

References 23 publications

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“…Studies from our laboratories have also demonstrated major shifts in total Ig synthesis, including profound enhancement, in coculture experiments with PBL from normal donors and patients with hypogammaglobulinemia (31). By contrast, however, other investigators have demonstrated highly restricted suppressor activity, including suppression of specific Ig allotypes (11,12), idiotypes (13,14), class (15), and antibodies (16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 97%

Suppression of immunoglobulin synthesis and secretion by peripheral blood lymphocytes from normal donors.

Schwartz¹,

Shou²,

Good³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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Concanavalin A (Con A)treated peripheral blood lymphocytes from healthy volunteer donors have been shown to suppress proliferative responses associated with thymusderived lymphocytes (T-cells). The present investigations demonstrate that peripheral blood lymphocytes incubated with Con A for 48 hr can abrogate pokeweed mitogen-stimulated differentiation of bone-marrow-derived (B) lymphocytes to immunoglobulin-synthesizing and -secreting plasma cells. This effect was manifested when washed Con A-treated peripheral blood lymphocytes were added to pokeweed mitogen-stimulated cocultures containing fresh autologous or allogeneic mononuclear cells, and it did not appear to involve cytotoxicity. Parallel control cultures consisting of mononuclear leukocytes incubated for 48 hr in the absence of Con A also had immunoglobulin suppressor activity in mixing experiments. This effect, however, was most pronounced when preincubated cells were added to fresh autologous pokeweed mitogen-stimulated peripheral blood lymphocytes. Cell mixtures containing peripheral blood lymphocytes incubated in the absence of Con A plus fresh allogeneic lymphocytes demonstrated a spectrum of immunoregulatory effects ranging from suppression to enhancement of pokeweed mitogen-stimulated immunoglobulin synthesis and secretion. Several functional subclasses of suppressor cells that reflect varying levels of specific activity have thus been demonstrated in human beings. Moreover, a degree of genetic identity appears to be required for the expression of "weak" immunoregulatory influences.

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Section: Discussionmentioning

confidence: 97%

Suppression of immunoglobulin synthesis and secretion by peripheral blood lymphocytes from normal donors.

Schwartz¹,

Shou²,

Good³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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“…As the source of antigen-specific suppressor T cells, mice were immunized with two intraperitoneal injections of 100 /~g soluble KLH at a 2-wk interval as described previously (8). Other mice were immunized with 100/~g of DNP-KLH or KLH alone in aluminum hydroxide gel (alum) together with 1 × 109 killed Bordetella pertussis vaccine.…”

Section: Methodsmentioning

confidence: 99%

“…Keyhole limpet hemocyanin (KLH) was obtained from Calbiochem, San Diego, Calif. Dinitrophenylated KLH (DNPT~o-KLH) was prepared by the method described previously (8). Egg albumin recrystallized five times was purchased from Nutritional Biochemicals Corporation, Cleveland, Ohio.…”

Section: Methodsmentioning

confidence: 99%

Specific enrichment of the suppressor T cell bearing I-J determinants: parallel functional and serological characterizations.

Okumura¹,

Takemori²,

Tokuhisa³

et al. 1977

The Journal of Experimental Medicine

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101

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Recent evidence indicates that determinants controlled by a locus (Ia-4 locus) mapped in I-J subregion of mouse H-2 major histocompatibility complex are selectively expressed on a functional subpopulation of peripheral T lymphocyte, which is endowed with a role to suppress the antibody and immunoglobulin production (1-3). 1 Unlike other/-region associated (Ia) antigens, which are primarily detectable on B cells, the products of Ia-4 locus are not found on B cells, but are uniquely expressed on T cells (1, 4). In addition, the same locus in I-J subregion appears to control the determinants found on the antigenspecific suppressive T-cell factor (3), and thus I-J subregion products provide an important clue for studying the nature of both the Ia antigen and the antigen-receptor which are unique to T cells.However, the presence of such/-region determinants on T cells has been mainly determined by functional analyses in which the activity of suppressor T-cell and suppressive T-cell factor is removed by anti-Ia antisera (1, 3, 5, 6), and no direct serological affirmation for the T-cell Ia antigen is yet available using standard cytotoxic assays. This is probably due to the fact that only a very small portion of T cells among total lymphoid cells express such Ia antigens, and this imposes a great limitation in determining the specificity, function, and biochemical structure of T-cell Ia antigens.We have reported in a preliminary form a simple technique to enrich the antigen-specific suppressor T cell which carries I-J subregion determinants (7). We confirmed further that this method is highly effective in obtaining antigenspecific T cells and in analyzing their phenotypic expressions by the usual serological procedures. This report will describe the detailed method to enrich the I-J-bearing suppressor T cell, and the serological and functional analyses of the purified suppressor T cell and its products. We also present our recent results concerning the relationship between the I-J determinants, Lyt phenotype, and Fc receptor (FcR) ~ expressed on the specifically purified suppressor T cell.

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“…Furthermore, based on the Ia specificities examined, both the I-A (Ia.1, 3, 15) and I-C (Ia.7) subregions (2) should contain glycosyl transferase genes. Second, the close relationship between Ia antigens and many T-cellderived immunoregulatory substances (10)(11)(12) suggests that carbohydrates may play a role in T-B cell collaboration. Finally, the fact that Ia antigens are oligosaccharide in nature must be borne in mind when attempts are made to develop a relationship between Ia antigens and Ir genes and their role as recognition units.…”

Section: Inhibition Of Anti-ia3 By D-galactose and Related Sugarsmentioning

confidence: 99%

Ia antigenic specificities are oligosaccharide in nature: hapten-inhibition studies.

Clarke¹,

Parish²

1977

The Journal of Experimental Medicine

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The Ia (I region associated) antigenic system in the mouse is coded for by genes located within the H-2 complex and consists of at least four subregions (IA, IB, IE, AND IC) which code for a minimum of 21 (Ia. 1 to 21) specificities (1-3), although the existence of IB and IE subregions is now being questioned. These antigens were first detected on the surface of B lymphocytes and were subsequently found on macrophages, epidermal cells, and sperm cells (4). It is also apparent that some Ia specificities are present on either resting and activated T-blast cells (2-8). In addition, we have detected considerable amounts of Ia antigenic material in mouse serum and other tissue fluids, particularly after antigenic stimulation (8, 9). The current interest in this system stems from the close involvement of the I region in immune responses (1-3), especially with the recent demonstration that soluble factors of both antigen-specific and nonspecific nature which are involved in T-B cell collaboration (10, 11) and suppression (12), also carry Ia antigens. In this context, we have found that although B cells have a higher density of Ia antigens on their surface than T cells, the Ia antigens in serum are derived from T cells (9).Biochemical studies of the Ia specificities have proceeded along two lines. The cell surface Ia antigens of B cells have been extracted with detergents and were found to be glycoproteins with mol wt of approximately 30,000 (13,14). By contrast, our chemical studies of the serum Ia material suggest that it is predominantly (but not exclusively) carbohydrate in nature as the material has the following properties: (a) It is rich in carbohydrate and almost devoid of protein (15); (b) The Ia antigenicity is destroyed by neuraminidase and periodate, but not by pronase (15); (c) The Ia antigen binds to concanavalin A and Lotus lectins (15); (d) It is extracted and purified from serum by methods identical to those used to prepare oligosaccharides from human milk (15-17); (e) Its behaviour on paper and thin layer chromatography is similar to that of other oligosaccharides (15), and after acid hydrolysis of the purified Ia product a number of simple sugars have been detected by gas-liquid chromatography (manuscript in preparation). In this paper, we describe hapten inhibition studies using a variety of sugars that show that for at least four Ia antigens (Ia.1, Ia.3, Ia.7, and Ia.15) the antigenic specificity is defined by sugars.

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Properties of antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. I. In vivo activity and immunochemical characterization.

Cited by 170 publications

References 23 publications

Suppression of immunoglobulin synthesis and secretion by peripheral blood lymphocytes from normal donors.

Suppression of immunoglobulin synthesis and secretion by peripheral blood lymphocytes from normal donors.

Specific enrichment of the suppressor T cell bearing I-J determinants: parallel functional and serological characterizations.

Ia antigenic specificities are oligosaccharide in nature: hapten-inhibition studies.

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