scholarly journals THE ABILITY OF BACTERIAL LIPOPOLYSACCHARIDE TO MODULATE THE INDUCTION OF UNRESPONSIVENESS TO A STATE OF IMMUNITY

1973 ◽  
Vol 138 (6) ◽  
pp. 1481-1495 ◽  
Author(s):  
J. A. Louis ◽  
J. M. Chiller ◽  
W. O. Weigle
Keyword(s):  
T Cell ◽  
Temporal Relationship ◽  
Gamma Globulin ◽  
Bacterial Lipopolysaccharide ◽  
Secondary Response ◽  
Transfer System ◽  
Primary Antibody Response ◽  
Human Gamma Globulin ◽  
Cell Cooperation ◽  
Induction Of Tolerance

Studies were performed to define the cellular parameters involved in the interference with the induction of immunologic unresponsiveness to human gamma globulin (HGG) by bacterial lipopolysaccharide (LPS). Mice which were injected with deaggregated HGG (tolerogen) and with LPS did not become tolerant to that antigen, but rather became primed to a subsequent challenge with immunogen. The ability to prime with tolerogen and LPS was also demonstrated in an adoptive transfer system. The temporal relationship between the injection of tolerogen and that of LPS was critical for priming to occur. The injection of tolerogen and LPS not only primed mice to HGG, but also resulted in a primary antibody response to HGG. The capacity of LPS to interfere with the induction of tolerance was restricted to B cells and did not affect the ability to induce unresponsiveness in T cells. The secondary response to HGG in mice primed by tolerogen and LPS was found to be T-cell independent. These observations are interpreted and discussed from the standpoint of the ability of LPS to circumvent required T-cell cooperation and to modulate to tolerogenic stimulus into an immunogenic signal.

scholarly journals Suppressor T cell memory. II. The role of memory suppressor T cells in tolerance to human gamma globulin.

1983 ◽  
Vol 157 (3) ◽  
pp. 957-973 ◽  
Author(s):  
R H Loblay ◽  
B Fazekas de St Groth ◽  
H Pritchard-Briscoe ◽  
A Basten
Keyword(s):  
T Cell ◽  
Low Dose ◽  
Gamma Globulin ◽  
Tolerance Induction ◽  
Secondary Response ◽  
High Dose ◽  
Suppressor T Cell ◽  
Specific Effects ◽  
Human Gamma Globulin ◽  
Dose Tolerance

The transient presence of suppressor T cell (Ts) activity in high-dose tolerance to human gamma globulin (HGG), and its (apparent) absence in low-dose tolerance, have been advanced as strong evidence against the concept that Ts play an important role in maintenance of immunological unresponsiveness. To analyze this question, CBA mice were exposed to high or low doses of deaggregated HGG (dHGG) and later challenged with HGG in immunogenic form (aHGG); their capacity to mount a primary or secondary suppressive response was assessed in an adoptive hapten-carrier system. Primary suppression reached a maximum 7 d after high-dose tolerance induction and gradually waned thereafter, being no longer detectable by day 30-35. Subsequent challenge of tolerant mice with aHGG, however, led to a rapid reactivation of suppression that bore the hallmarks of an anamnestic secondary response, and this effect was still demonstrable 135 d after tolerance induction. It was also shown that a single low dose of dHGG was capable of generating memory for suppression despite the absence of detectable primary suppression, indicating that the latter is not a prerequisite for induction of memory cells. The results were interpreted as indicating that tolerance, like immunity, is a manifestation of specific immunological memory. If tolerance to self-antigens is maintained by a similar mechanism, it would be expected that memory Ts could be induced during the early stages of fetal development. Mice were therefore exposed to tolerogen in utero by injection of their mothers with dHGG at day 7 of gestation, and were assessed at various times after birth for the capacity to exhibit primary or secondary suppression in adoptive transfer. Nonspecific suppression masked any specific effects during the first 5 wk of life. Antigen-specific, primary suppression was demonstrable subsequently until 10-12 wk of age, and if the animals were challenged with aHGG before transfer an anamnestic secondary suppressive response could be elicited up to 6 mo of age. These observations are consistent with the notion that memory Ts may play an important role in the maintenance of self-tolerance.

scholarly journals The requirement for C3 receptors on the precursors of 19S and 7S antibody-forming cells.

1976 ◽  
Vol 143 (5) ◽  
pp. 1111-1121 ◽  
Author(s):  
D W Mason
Keyword(s):  
T Cell ◽  
B Cells ◽  
Antibody Response ◽  
B Cell ◽  
Adoptive Transfer ◽  
Thoracic Duct ◽  
Transfer System ◽  
C3 Receptors ◽  
Cell Cooperation

The main conclusion from this study is that C3 receptors are not required for the generation from B cells of a thymus-dependent 7S antibody response. The requirement for C3 receptors on the precursors of antibody-forming cells was studied in an adoptive transfer system using thoracic duct lymphocytes (TDL) from primed rats as a source of precursors and irradiated recipients as hosts. 7S precursors were found in both the CR+ and the CR- fractions of TDL and it was established that the response transferred by CR- cells did not arise from either a raidoresistant B cell in the host or from CR+ cells contaminating the CR- population. Thus, the C3 receptor is not obligatory for B-cell-T-cell cooperation in the 7S response. The precursors of 19S antibody-forming cells were found only in the CR+ subpopulation. The CR-Ig+ subpopulation was shown to contain all the B blasts in rat TDL and a very small number (approximately 1% of all TDL) of small lymphocytes. This latter population contained the CR- 7S precursors and contributed approximately 20% of the total adoptive secondary 7S response transferred by CR+ and CR- subpopulations combined. This observation suggests that the percentage of rat TDL committed to carry 7S memory is small, a conclusion which is confirmed and extended in the following paper.

scholarly journals THE REQUIREMENT OF MORE THAN ONE ANTIGENIC DETERMINANT FOR IMMUNOGENICITY

1969 ◽  
Vol 129 (6) ◽  
pp. 1131-1143 ◽  
Author(s):  
K. Rajewsky ◽  
V. Schirrmacher ◽  
S. Nase ◽  
N. K. Jerne
Keyword(s):  
Bovine Serum Albumin ◽  
Bovine Serum ◽  
Antigenic Determinant ◽  
Antibody Formation ◽  
Gamma Globulin ◽  
Sulfanilic Acid ◽  
Secondary Response ◽  
Acid Complex ◽  
Human Gamma Globulin ◽  
Secondary Stimulus

Rabbits primarily stimulated with a BSA (bovine serum albumin)-sulfanilic acid complex will produce a good secondary response to the sulfanilic acid hapten if the carrier used in the secondary stimulus is again BSA, and not if the secondary carrier is HGG (human gamma globulin). In the latter situation, a good secondary response is obtained, however, if the rabbits are pretreated a few weeks earlier with free HGG. We conclude that the immune stimulus involves the recognition of carrier determinants unrelated to the hapten. As the receptors for recognition of unrelated determinants are probably situated on different cells, we suggest that the immune stimulus leading to antibody formation requires the interaction of two antigen-bridged cells.

scholarly journals Induction and mode of action of suppressor cells generated against human gamma globulin. II. Effects of colchicine.

1979 ◽  
Vol 149 (5) ◽  
pp. 1168-1182 ◽  
Author(s):  
D E Parks ◽  
D A Shaller ◽  
W O Weigle
Keyword(s):  
Cell Response ◽  
Mode Of Action ◽  
Soluble Protein ◽  
B Lymphocyte ◽  
Gamma Globulin ◽  
Suppressor Cells ◽  
Observable Effect ◽  
Human Gamma Globulin ◽  
Lymphocyte Populations ◽  
Induction Of Tolerance

The ability of colchicine (Col) to interfere with suppressor cells specific for the soluble protein antigen human gamma globulin (HGG) has been examined. This interference may be the mechanism of the adjuvanticity promoted by Col. When injected into A/J mice at the appropriate time and concentration, both Col and cyclophosphamide promoted an adjuvant increase in the plaque-forming cell response to 100 micrograms of immunogenic, aggregated HGG. Col abrogated both the induction of suppressor cells when injected with 3 h of tolerization with deaggregated (DHGG) and the expression of previously induced suppressor cells when injected with the antigenic challenge. Interference with the generation and expression of antigen-specific suppressor cells had no detectable effects on the immunologic unresponsive state to HGG. Col did not interfere with the induction of tolerance at a dose (1 mg/kg) that abolished the generation of suppressor cells. Furthermore, the absence of colchicine-sensitive-suppressor cells during the establishment of tolerance had no observable effect on the duration of unresponsivness in either helper T- or B-lymphocyte populations. Finally, Col was not able to terminate the unresponsive state established by DHGG even when responsive splenic B cells could be demonstrated in tolerant animals. These data indicate that suppressor cells are not required for the establishment and maintenance of the unresponsive state to this antigen.

scholarly journals Isolated hapten-binding receptors of sensitized lymphocytes. III. Evidence for idiotypic restriction of T-cell receptors.

1978 ◽  
Vol 147 (5) ◽  
pp. 1341-1347 ◽  
Author(s):  
U Krawinkel ◽  
M Cramer ◽  
I Melchers ◽  
T Imanishi-Kari ◽  
K Rajewsky
Keyword(s):  
T Cell ◽  
B Lymphocytes ◽  
Heavy Chain ◽  
T Cell Receptors ◽  
Germ Line ◽  
Secondary Response ◽  
Antigen Receptors ◽  
Primary Antibody Response ◽  
V Genes ◽  
Antibody Population

The primary antibody response of C57BL/6 mice to the 4-hydroxy-3-nitrophenylacetyl (NP) hapten is restricted to antibody molecules expressing the NPb idiotype. This idiotype is a genetic marker for V genes in the heavy chain linkage group. In the secondary response, the frequency of NPb idiotype-positive molecules within the antibody population drops to very low values. Accordingly, isolated NP binding receptors from NP-sensitized B lymphocytes are largely devoid of this idiotype. In contrast, the NPb idiotype is expressed on the majority of the receptor fractions which we consider T-cell derived. This finding suggests that the antigen receptors of T lymphocytes may be restricted to the expression of major (germ-line encoded?) heavy chain idiotypes.

scholarly journals B-cell tolerance. II. Trinitrophenyl human gamma globulin-induced tolerance in adult and neonatal murine B cells responsive to thymus- dependent and independent forms of the same hapten

1977 ◽  
Vol 145 (3) ◽  
pp. 778-783 ◽  
Author(s):  
JC Cambier ◽  
ES Vitetta ◽  
JW Uhr ◽  
Kettman JR
Keyword(s):  
B Cells ◽  
B Cell ◽  
Gamma Globulin ◽  
Tolerance Induction ◽  
Cell Tolerance ◽  
B Cell Tolerance ◽  
Adult Mice ◽  
Human Gamma Globulin ◽  
Induction Of Tolerance

Neonatal splenic B cells which are responsive to thymus-dependent antigens (TD) are exquisitely susceptible to induction of tolerance (1,2). This state of tolerance is not mediated by suppressor T cells and is not a result of suboptimal macrophage function (1 and footnote one). In adult mice, induction of B-cell tolerance is not achieved with doses of antigen 1,000-fold higher (1) than those required to produce the same degree of unresponsiveness in neonates. In contrast to these results, studies with T-independent (TI) antigens indicate that neonatal and adult splenic B cells are equally susceptible to tolerance induction (3,4). However, such studies have not ascertained whether the neonate is more resistant to tolerance induction or the adult is hypersusceptible, i.e., does the induction of tolerance in cells responsive to TI antigens resemble that of adult or neonatal cells responsive to TD antigens? The answer is pertinent to determining the relative maturity of the B cells which can be tolerized or respond to TI or TD antigens. We report here the direct comparison of tolerogen sensitivity of adult and neonatal TD and TI responses by inducing tolerance in vitro with trinitophenyl human gamma globulin (TNP(17)HgG) and assaying unresponsiveness with TD and TI forms of the TNP determinant.

scholarly journals Definition of conditions that enable antigen-specific activation of the majority of isolated trinitrophenol-binding B cells.

1982 ◽  
Vol 156 (6) ◽  
pp. 1635-1649 ◽  
Author(s):  
J C Cambier ◽  
J G Monroe ◽  
M J Neale
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
Interleukin 1 ◽  
Isolated Cells ◽  
Cellular Events ◽  
Accessory Cells ◽  
B Cell Growth Factor ◽  
Human Gamma Globulin ◽  
Definition Of ◽  
T Cell Help

In an effort to further elucidate the early cellular events in generation of antibody responses, we have determined the requirements for antigen-specific initiation of the G0 to G1 transition by isolated trinitrophenol (TNP) -binding B lymphocytes. TNP-binding cells were isolated from normal B6D2F1 splenocyte populations using hapten affinity fractionation on disulfide-bonded TNP-gelatin-coated plates. Populations prepared in this way are greater than or equal to 96% immunoglobulin positive and 70-95% antigen binding. Isolated cells were cultured for 48 h in the presence of a variety of TNP conjugates including TNP-Brucella abortus (Ba), TNP-Ficoll, TNP-sheep erythrocytes (SRBC), TNP-human gamma globulin (HGG), or TNP-ovalbumin (OVA) before being harvested and subjected to acridine orange cell cycle analysis. As many as 80% of cells were in cycle by 48 h in response to TNP-Ba, a thymus-independent (TI1 antigen. A smaller proportion (congruent to 40%) were in cycle in response to TNP-Ficoll, a TI2 antigen. Significant activation was not detected in cultures challenged with the thymus-dependent immunogens TNP-SRBC, TNP-HGG, and TNP-OVA. Addition of interleukin 1 (IL-1), IL-2, B cell growth factor, and/or T cell-replacing factor to cultures did not facilitate responses to these immunogens, suggesting a requirement for antigen-specific T cell help for entry into cell cycle induced by thymus dependent antigens. Activation by TNP-Ba was antigen specific and independent of accessory cells, occurring with equal efficiency in bulk and single-cell cultures. Activation by TNP-Ba was inhibitable by anti-Fab and anti-mu antibodies, but not by anti-delta antibodies. Results indicate that activation of TNP-binding cells to enter cell cycle by TNP-Ba is independent of accessory cells and requires interaction of antigen with cell surface IgM. Exposure to thymus-dependent TNP-immunogens plus nonspecific helper factors is insufficient to cause entry of TNP-binding cells into cycle.

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