Conditions Determining the Generation and Expression of T Helper Cells

Waldmann, Herman

doi:10.1111/j.1600-065x.1977.tb00238.x

Cited by 62 publications

(37 citation statements)

References 30 publications

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“…Additional evidence in humans supporting the concept of heterogeneity at the T-cell level is data in the present studies and those of other investigators indicating that macrophages are not important to generate mitogenactivated suppressors that regulate Ig production (22) and that non-T cells are not required to generate Con A-activated suppressors that regulate the blastogenic response (15,23). That regulatory populations may indeed derive from different T-cell pools has also been suggested by others (24,25). Tada et al (24), in particular, have demonstrated in an antigen-activated helper cell system that distinct types of helper cells (Ly 1, Ia-or Ly 1, Ia+) were activated depending on whether the hapten and carrier were in one molecule or separate.…”

Section: Discussionmentioning

confidence: 57%

Inhibition of humoral and cell-mediated immune responses in man by distinct suppressor cell systems.

Lobo¹,

Spencer²

1979

J. Clin. Invest.

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A B S T R A C T Studies were designed to investigate whether the suppressor cell systems that regulate the humoral and cell-mediated immune responses belong to the same subsets ofT cells or different subsets. Mitogen-activated suppressor cells were simultaneously assayed for their ability to inhibit (a) pokeweed mitogeninduced generation of plasma cells, (b) blastogenic response of lymphocytes to allogeneic cells, and (c) generation of killer cells in the cell-mediated lymphocytotoxicity assay. We found that suppressor cells that inhibited the generation of plasma cells were activated by concanavalin A (Con A) and were both radiation and prednisone sensitive. Suppressors that inhibited the blastogenic response in lymphocytes to allogenic cells were also activated by Con A but differed in that they were both radiation and prednisone resistant. In contrast, suppressors that inhibited the generation of the killer cells were activated with phytohemagglutinin and not Con A. These suppressors were prednisone andl radiation resistant. These observations cannot be explained by differences at the pro-suppressor or suppressor activator levels as both T cell subsets are radiosensitive. Alternatively, heterogeneity of suppressor cell systems may explain these differences.

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Section: Discussionmentioning

confidence: 57%

Inhibition of humoral and cell-mediated immune responses in man by distinct suppressor cell systems.

Lobo¹,

Spencer²

1979

J. Clin. Invest.

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“…At present it is not clear that one can talk of a single molecular entity in the case of TRF or NSF. However, current molecular weight estimations suggest that all activity is found in the range of 25 000-40 000 daltons (Waldmann 1977). Undoubtedly these factors act across strain barriers.…”

Section: Two Subpopulations Ofhelper T Cellsmentioning

confidence: 99%

“…Secondly, it has recently become possible to generate populations of helper T cells which can cooperate well nonspecifically, but poorly in linked recognition systems. This has been achieved by priming with very low doses of antigen (Marrack & Kappler 1976, Waldmann 1977 (Phillips & Waldmann 1977) or by measuring responses to two different haptens on the same protein carrier (Waldmann, Kenny et al 1979). Activation of more than one B cell would be predicted were cooperation mediated by widely diffusible factors.…”

Section: Two Subpopulations Ofhelper T Cellsmentioning

confidence: 99%

“…There are two reasons why such cells cooperate poorly. First, the MHC differences provoke cells which are active inhibitors of antibody production (Waldmann 1977). Differences in the serologically defined determinants (K and D ends in the mouse) are particularly potent in this respect.…”

Section: Genetic Restrictions In T-b Cell Interactionsmentioning

confidence: 99%

“…Alternatively, such inhibitory cells may be true suppressor T cells. Nevertheless, such cells can be eliminated by pretreatment of the potential helper cell population by irradiation (Waldmann 1977), mitomycin treatment (Swain et al 1977), negative selection procedures or by induction of tolerance in the T cell donor . The potency of inhibition in such allogeneic T-B mixtures gives a warning to all forms of experiment in the human system where suppressor status is determined by mixing cells from different donors.…”

Section: Genetic Restrictions In T-b Cell Interactionsmentioning

confidence: 99%

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Interactions between T and B Cells: A Review

Waldmann

1979

J R Soc Med

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The problem of how T and B lymphocytes interact in antibody formation is one fundamental to the full understanding of many immune deficiency diseases. One can hope that as the mechanisms for cooperation become resolved then so, too, will a new range of diagnostic approaches develop to pinpoint particular defects.In this article I wish to select certain growing points in mouse T-B immunology which I feel offer a working bridge to the human system. Three areas will be considered:(1) The cellular basis of the interaction.(2) The status of helper and suppressor factors in cell interactions.(3) The current status of our understanding of the requirements for genetic identity within the major histocompatibility complex (MHC) of interacting T and B cells.

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The specificity of nonspecific concanavalin A‐induced helper factors

Bemabé

Martínez-Alonso

Coutinho³

1979

Eur J Immunol

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Addition of supernatants from concanavalin A (Con A)-stimulated spleen cells enable nude spleen cells to respond in vitro to a variety of antigens (in our experiments, sheep (SRBC) and horse erythrocytes (HRBC)). Experiments presented here, indicate that such nonspecific helper supernatants are in fact a polyclonal mixture of diverse, specific activities. Con A stimulation of thoracic duct lymphocytes, specifically depleted of SRBC or HRBC-reactive cells by the Sprent technique, results in a specific decrease in the activity to the relevant antigen. On the one hand, Con A stimulation of in vivo activated thymocytes results in the production of helper supernatants which are almost totally specific for the antigen used in priming.In spite of these indications of specificity, it has been impossible to absorb out helper activity from normal Con A supernatants on the corresponding antigen. Specific removal of helper activity, however, can readily be achieved by absorbing helper supernatants on complexes of antigen and early immune sera. Various control experiments demonstrate that the loss of activity in the absorbed supernatants is not due to carry-over of antibody into the test cultures. Furthermore, the fraction of helper activity that can be specifically removed on antigen-antibody complexes depends on the conditions used in the preparation of the supernatants; this fraction is highest when Con A activation of T cells is performed in the presence of B cells without antigen .These results suggest that "nonspecific helper factors" are a mixture of diverse molecules, some of which show specificity for variable regions of antibodies.

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Conditions Determining the Generation and Expression of T Helper Cells

Cited by 62 publications

References 30 publications

Inhibition of humoral and cell-mediated immune responses in man by distinct suppressor cell systems.

Inhibition of humoral and cell-mediated immune responses in man by distinct suppressor cell systems.

Interactions between T and B Cells: A Review

The specificity of nonspecific concanavalin A‐induced helper factors

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