Competition between concanavalin A-induced stimulatory and inhibitory effects in the in vitro immune response to antigen.

Scavulli, John F.; Dutton, Richard

doi:10.1084/jem.141.2.524

Cited by 27 publications

(16 citation statements)

References 11 publications

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“…Our data do not distinguish whether the effect of cellular concentration and period of cultivation on the response when cells are mixed is mediated directly by cell-cell interaction or via factors in the medium. The present work underlines the difficulty of interpretation and prediction of results in studies of the interactions between cell types in which different ratios of cells are mixed without also varying the total cell concentration or in which more than two sources of cells are mixed (43). Finally, this work illustrates that the function of cells ascertained in one set of conditions need not apply in a different cellular environment.…”

Section: Figurementioning

confidence: 90%

Help and suppression by lymphoid cells as a function of cellular concentration.

Farrant¹,

Knight²

1979

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

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The phytohemagglutinin-stimulated uptake When lymphocyte populations are mixed, both T cells and B cells may promote or impede their interaction ("helper" and "suppressor" functions, respectively) (1-13). It is known that lymphocyte function is related to cellular concentration in vitro both for thymidine uptake (5,8,11,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) and for other responses (6,7,11,17,19,22,(26)(27)(28)(29)(30)(31)(32)(33)(34). According to the "quantal theory" of Brent and Medawar (35), the changing sensitivity of the lymphocyte population in vivo is a function of the numbers of active cells rather than of a changing sensitivity of individual cells. Some helper and suppressor effects when cells are mixed may therefore vary with cellular concentration. Coutinho and Moller (36) have described a mechanism for suppression that involves an "excess of help" as the numbers of added cells are increased. A more general view that helper and suppressor effects are mediated through different populations of cells is based primarily on the unequal susceptibility of help and suppression to damaging treatments by antisera [e.g., anti-Ly sera (4, 7, 10, 37-39)], by x-irradiation (1, 12, 22, 29, 40), or by mitomycin C (13, 22, 40).We have now studied in more detail than hitherto (23, 24) the effects of cellular concentrations in culture on DNA synthesis in normal human peripheral lymphocytes stimulated with phytohemagglutinin (PHA) and in human lymphoid cell lines believed to be monoclonal. The data show that both helper and suppressor effects can be demonstrated when cells are mixed, even when the cells participating are from the same monoclonal cell line. This fits a hypothesis that help and suppression are mediated through the altered concentrations of cells. Fig. 1 shows the effect of initial cell concentration in culture on the uptake of [3H]thymidine into human peripheral lymphocytes stimulated with PHA for 96 hr with no mitomycintreated cells present. The incorporation was low with 2.5 X 104 cells per ml, maximal with 6 X 105 cells per ml, and lower than maximal at higher cell concentrations. From this curve, the response at each cell concentration can be considered to come from mixtures of cells even though the samples were from a single source of lymphocytes (not treated with mitomycin). For example, addition of 2.5 X 105 cells per ml to a sample containing very few cells (4 X 104 cells per ml) will cause a great increase in uptake over the response of 4 X 104 cells per ml alone and yet the same 2.5 X 105 cells per ml added to 6 X 105 cells per ml or more will not increase the response and may decrease it. Thus, even the direction of the effect of addition of a sample depends on the cellular concentration. Fig. 1 also shows that the response of a sample of cells can be modified by mixing it with cells treated with mitomycin C. When 2.5 X 104 cells per ml were mixed with 2.5 X 105 mitomycin-treated cells per ml the level of incorporation increased, mixing with more mitomycin-treated cells decrea...

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Section: Figurementioning

confidence: 90%

Help and suppression by lymphoid cells as a function of cellular concentration.

Farrant¹,

Knight²

1979

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

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“…However, similar experiments performed by Dutton (1973) led to different conclusions, based mainly on the fact that irradiation selectively eliminated suppressor but not helper T cells. Although it could be argued that irradiation simply reduced the number of T cells, it was later shown that this was not tbe case as dilution of the suppressor cells did not result in the appearance of helper effects (Scavulli & Dutton 1975).…”

mentioning

confidence: 99%

Lymphocyte‐Mediated Cytotoxicity Against Tumor Cells Specificity and Characterization of Concanavalin A‐Activated Cytotoxic Effector Lymphocytes

Waterfield

Anaclerio

et al. 1976

Immunological Reviews

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“…In addition HSA, an antigen without nonspecific mitogenic properties, had n o effect when injected simultaneously with AHGG. Nor can these results be explained by the production of a helper and suppressor T cell population, widely reported to be generated on lectin treatment [17][18][19][20] since Con A decreased AHGG trapping in the spleen of T celldeprived mice as well as normal mice (Table 4), and also because decreased uptake was found as early as 2 h after simultaneous injections of Con A and AHGG (Table 3), probably before any blast transformation occurred.…”

Section: Discussionmentioning

confidence: 99%

Reduction of trapping of aggregated human IgG in germinal centers by mitogens

et al. 1976

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The effect of nonspecific mitogens on the trapping of 125I-labeled aggregated human IgG (125I-AHGG) in germinal centers (GC) of mouse spleens has been investigated by both radioactivity uptake and immunofluorescence. Phytohemagglutinin and concanavalin A (Con A) significantly decreased trapping. Lipopolysaccharide produced less inhibition, and pokeweed mitogen had no significant effect. The maximum inhibition occurred with 250--500 mug Con A. This had no effect on 125I-AHGG uptake in liver kidney and blood. No differences were found between i.p. and i.v. routes of Con A injection. The effect of mitogens on the 125I-AHGG trapping in GC is due more likely to modification of the migratory properties of lymphocytes brought about by surface binding, than to their mitogenic properties, since Con A decreased 125I-AHGG localization in thymectomized, x-irradiated and bone marrow-reconstituted animals.

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Competition between concanavalin A-induced stimulatory and inhibitory effects in the in vitro immune response to antigen.

Cited by 27 publications

References 11 publications

Help and suppression by lymphoid cells as a function of cellular concentration.

Help and suppression by lymphoid cells as a function of cellular concentration.

Lymphocyte‐Mediated Cytotoxicity Against Tumor Cells Specificity and Characterization of Concanavalin A‐Activated Cytotoxic Effector Lymphocytes

Reduction of trapping of aggregated human IgG in germinal centers by mitogens

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