The Sheep Erythrocyte T-Dependent Antibody Response (TDAR)

Infection of mice with the murine sarcoma virus (Moloney) markedly suppressed the humoral antibody response to sheep erythrocyte antigen injected 10 days after infection, when tumor size was maximal, and on day 26, when primary tumors had partially regressed. Humoral antibody response was also inhibited when antigen was injected at the time secondary tumors and metastases were evident. No significant suppression of humoral antibody was seen when mice were injected with sheep erythrocyte antigen 5 days after virus infection. Inhibition of the cellular immune response of murine sarcoma virus (Moloney)-infected mice, as measured by the increased survival time of skin grafts, was also determined. Mice that were infected 5 days prior to grafting demonstrated prolonged survival of grafts, suggesting a suppression of cellular immunity. These mice had a graft survival time 14 days greater than noninfected controls. No significant prolongation of graft survival was seen in mice grafted at the times of maximum primary tumor growth, of primary tumor regression, or when secondary tumors had appeared.

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REGULATION OF ANTIBODY RESPONSE BY CELLS EXPRESSING HISTAMINE RECEPTORS

Journal of Experimental Medicine ◽

10.1084/jem.136.5.1302 ◽

1972 ◽

Vol 136 (5) ◽

pp. 1302-1307 ◽

Cited By ~ 96

Author(s):

G. M. Shearer ◽

Kenneth L. Melmon ◽

Yacob Weinstein ◽

Michael Sela

Keyword(s):

Immune Response ◽

Antibody Response ◽

Serum Albumin ◽

Sheep Erythrocyte ◽

Antibody Responses ◽

Rabbit Serum ◽

Spleen Cells ◽

Surface Receptors ◽

Cell Responses ◽

A Cell

Spleen cells from immunized and unimmunized mice were either passed over histamine-rabbit serum albumin-Sepharose columns or rabbit serum albumin-Sepharose control columns. The immune response potential of 5 x 106 cells excluded from the two columns were compared with each other, and with an equal number of unfiltered cells by injection of the cell suspensions mixed with sheep erythrocytes into irradiated, syngeneic recipients. The direct and indirect anti-sheep erythrocyte plaque-forming cell responses generated by the cells passed over the histamine-bead column were significantly greater than the responses resulting from the inocula of unfiltered cells or cells passed over control columns. These results indicate the existence of a cell population expressing surface receptors for histamine, which functions to regulate antibody responses.

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HOMEOSTASIS OF ANTIBODY FORMATION IN THE ADULT RAT

Journal of Experimental Medicine ◽

10.1084/jem.120.6.987 ◽

1964 ◽

Vol 120 (6) ◽

pp. 987-1005 ◽

Cited By ~ 92

Author(s):

Donald A. Rowley ◽

Frank W. Fitch

Keyword(s):

Antibody Response ◽

Specific Antibody ◽

Antibody Formation ◽

Sheep Erythrocyte ◽

Passive Immunization ◽

Primary Antibody ◽

Secondary Response ◽

Primary Antibody Response

Passive immunization of rats with homologous anti-sheep erythrocyte serum markedly inhibited the primary antibody response to various doses of sheep erythrocytes. Inhibition was "specific" and apparently produced by either "19S" or "7S" antibody to the antigen. Passive immunization inhibited splenic hyperplasia associated with the primary antibody response. Passive immunization 24 hours after active immunization effectively inhibited the primary antibody response. The markedly suppressive effect of specific antibody on the primary antibody response contrasted sharply with the absence of this effect on the secondary response. Antigen-antibody complexes formed in vitro elicited no measurable primary antibody response but did elicit a high secondary response. Exposure of normal spleen cells to the antibody in vivo or in vitro suppressed their response to the antigen in x-irradiated recipients. In contrast, cells from previously immunized animals transferred to x-irradiated animals produced antibody in the presence of passively given antibody. Thus, "potential antibody-forming cells" from normal animals were unresponsive to the antigen in the presence of specific antibody, while "antibody-forming cells" from previously immunized animals responded to the antigen in the presence of antibody. Presumably, antibody actively produced in small quantities by a few antibody-forming cells might inhibit antibody formation by potential antibody-forming cells. Confirmation of this suggestion was obtained by showing that some animals initially injected with small doses of antigen failed to produce measurable antibody to subsequent injections of larger doses of the antigen. Low doses of antigen capable of inducing unresponsiveness produced no measurable circulating antibody, but these doses did produce increased numbers of plaque-forming (antibody-releasing) cells in spleens of rats. Thus, the formation of specific antibody may provide a homeostatic or "feed-back" mechanism which controls or limits production of specific antibody to the portion of the antibody-forming system previously stimulated by the antigen. This mechanism may account in part for immunological unresponsiveness produced in certain other related experimental systems.

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Immunoregulatory circuits that modulate responsiveness to suppressor cell signal. Failure of B10 mice to respond to suppressor factors can be overcome by quenching the contrasuppressor circuit.

Journal of Experimental Medicine ◽

10.1084/jem.153.6.1547 ◽

1981 ◽

Vol 153 (6) ◽

pp. 1547-1561 ◽

Cited By ~ 38

Author(s):

K Yamauchi ◽

D R Green ◽

D D Eardley ◽

D B Murphy ◽

R K Gershon

Keyword(s):

T Cells ◽

T Cell ◽

Antibody Response ◽

Sheep Erythrocyte ◽

Biologically Active ◽

Mouse Strains ◽

Cellular Interactions ◽

Spleen Cells ◽

Suppressor Factor

The in vitro antibody response of spleen cells from B10 strain mice is not suppressed by factor preparations made by primed Ly-2 T cells, although these preparations can suppress the in vitro antibody response of spleen cells from other mouse strains (1-3)2. The factor preparations from Ly-2 cells contain at least two separable activities: one that acts as a suppressor moiety (Ly-2 T cell suppressor factor [Ly-2 TsF]) and a second factor that acts as an inducer of contrasuppression (Ly-2 TcsiF); the latter initiates a series of cellular interactions that leads to the inhibition of suppression that we refer to as contrasuppression. Removal of components (either cellular or humoral) of the contrasuppressor circuit makes spleen cells from B10 strain mice as easily suppressible as are those of other mouse strains. Thus, removal of the contrasuppressor inducer cell and/or its biologically active product with the use of an anit-J serum, or removal of the functional acceptor of the inducer cell with the same or other (Ly-2; Qa-1) antisera breaks the B10 suppressor barrier. Contrasuppressive activity. but not helper activity can be eluted from anit-I-J immunoabsorbents. The addition of B10 T cells to either B6 or B10 spleen cell culture deprived of acceptor cells for the TcsiF reconstitutes contrasuppression more efficiently than does the addition of C57BL/6 T cells. Ly-2 TcsiF is more cross-reactive than is Ly-2 TsF so that absorption of factor preparations from sheep erythrocyte-primed Ly-2 cells with horse erythrocytes also breaks the B10 suppressor barrier. The hyperresponsiveness of splenic T cells from B10 strains to Ly-2 TcsiF may be an in vitro exaggeration of a normal in vivo process. Thus it is possible that one can take advantage of this unusual situation to help dissect out the cellular and subcellular components of T cell circuits that moldulate sensitivity to immunoregulatory signals.

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Antigen-specific T lymphocyte clones. III. Papain splits purified T suppressor molecules into two functional domains.

Journal of Experimental Medicine ◽

10.1084/jem.155.4.981 ◽

1982 ◽

Vol 155 (4) ◽

pp. 981-993 ◽

Cited By ~ 27

Author(s):

M Fresno ◽

L McVay-Boudreau ◽

H Cantor

Keyword(s):

Antibody Response ◽

T Lymphocyte ◽

Sheep Erythrocyte ◽

Variable Region ◽

Binding Activity ◽

Functional Domains ◽

Antigen Binding ◽

Constant Region ◽

Foreign Proteins

Purified molecules (70,000 mol wt) from a T-suppressor (Ts) clone bind to sheep erythrocyte glycophorin and specifically suppress the response to this antigen. Papain splits purified 70,000-mol wt Ts molecules into two peptides: mol wt 45,000 and 24,000. The 45,000-mol wt peptide nonspecifically suppresses antibody response to several antigens and lacks antigen-binding activity. The 24,000-mol wt peptide does not suppress but retains antigen-binding activity. The results indicate that papain splits the Ts molecule into a "constant" region responsible for function and a "variable" region responsible for antigen-binding. Since binding of the 70,000-mol wt molecule to antigen also results in release of the 45,000 mol wt subunit, this cleavage may allow Ts molecules specific for one determinant to suppress immunity to complex foreign proteins.

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Congenitally athymic nude (nu/nu) mice have Thy-1-bearing immunocompetent helper T cells in their peritoneal cavity.

Journal of Experimental Medicine ◽

10.1084/jem.151.4.965 ◽

1980 ◽

Vol 151 (4) ◽

pp. 965-968 ◽

Cited By ~ 36

Author(s):

H Ishikawa ◽

K Saito

Keyword(s):

T Cells ◽

Lymph Node ◽

Guinea Pig ◽

Antibody Response ◽

Sheep Erythrocyte ◽

Helper T Cells ◽

Spleen Cells ◽

Lymph Node Cells ◽

Pig Serum

Heavily irradiated peritoneal cells (PC) from congenitally athymic nude (nu/nu) mice markedly restored the impaired in vitro antibody response of nu/nu spleen cells to sheep erythrocyte antigens (T-dependent antigen), whereas irradiated spleen or lymph node cells from nu/nu mice had no effect on the response. This activity of the irradiated PC of nu/nu mice was completely abolished by treatment with anti-Thy-1.2 antiserum plus normal guinea pig serum (C') and is, therefore, attributable to a function of matured T cells.

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