Studies on T lymphocyte activation II. The target cells for concanavalin A‐induced growth factors

Coutinho, António; Larsson, Eva‐Lotta; Grönvik, Kjell-Olov; Andersson, Jan

doi:10.1002/eji.1830090803

Cited by 137 publications

(49 citation statements)

References 16 publications

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“…IL-2 Metabolism. In previous experiments, we (21) and others (22,23) had shown that cells expressing biologically active IL-2-R functioned to remove IL-2 from culture medium in a time-, temperature-, and cell concentration-dependent fashion. Subsequent findings (Cantreli, D. A., and K. A. Smith, manuscript in preparation) have shown that tbe depletion of IL-2 activity from the culture medium is due to a receptor-mediated internalization and degradation of IL-2 molecules that bind to the cells.…”

Section: Il-2-r Expression By T4 + Vs T8 + Cellsmentioning

confidence: 90%

Regulation of T cell autocrine growth. T4+ cells become refractory to interleukin 2.

Gullberg¹,

Smith²

1986

The Journal of Experimental Medicine

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During the course of investigating the regulation of IL-2-dependent T cell proliferation, we found that the subset of human T cells expressing the T4 surface glycoprotein become refractory to IL-2 growth promotion earlier than T8+ cells. Since T4+ cells proliferate in an autocrine fashion to endogenous IL-2, whereas most T8+ cells respond in a paracrine fashion to IL-2 derived from T4+ cells, we thought it likely that a unique mechanism was operative to restrict T4+ cell IL-2-dependent autocrine proliferation. Moreover, we anticipated that the T4+ cell IL-2-refractory state related either to suppression by T8+ cells, or to expression of T4+ cell IL-2-R. However, several experimental approaches did not support either of these mechanisms as being responsible for the loss of T4+ cell IL-2 responsiveness. Isolated T4+ cells ceased to respond to IL-2 well before T8+ cells, and before the disappearance of adequate levels of IL-2-R. Moreover, a detailed comparison of IL-2-R expression by T4+ vs. T8+ cells revealed no differences in the number, affinity, rate of expression, or functional activity of high-affinity IL-2-R expressed by the two subsets. Accordingly, T4+ cell autocrine IL-2 responsiveness is restricted by a mechanism that is independent of IL-2-R, and which ultimately results in cessation of both T4+ and T8+ cell IL-2-dependent clonal expansion.

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Section: Il-2-r Expression By T4 + Vs T8 + Cellsmentioning

confidence: 90%

Regulation of T cell autocrine growth. T4+ cells become refractory to interleukin 2.

Gullberg¹,

Smith²

1986

The Journal of Experimental Medicine

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“…Previous work indicated that T cell growth factor, or IL-2, does not trigger the growth of resting T cells (27,28). Rather, IL-2 acts in conjunction with other signals, or these cells must first be "activated" to respond to IL-2, a process which includes expression of functional receptors (28)(29)(30).…”

mentioning

confidence: 99%

Dendritic cells initiate a two-stage mechanism for T lymphocyte proliferation.

Austyn¹,

Steinman²,

Weinstein³

et al. 1983

The Journal of Experimental Medicine

112

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T cells oxidized with sodium periodate proliferate polyclonally in response to accessory cells. We confirmed previous work showing that DC are potent stimulators of this response. In addition, the accessory function of unfractionated mouse spleen and spleen adherent cells was markedly reduced after elimination of DC with a specific monoclonal antibody and complement. Therefore oxidative mitogenesis was used as a model to study the mechanism by which DC stimulate T cell proliferative responses. A two-stage mechanism was identified. The first stage occurred during the first 20 h of culture, required live DC, and involved the progressive release of interleukin 2 (IL-2) into the medium and acquisition of responsiveness to this growth factor. The second stage occurred between 20 and 40 h, did not require live DC, and involved DNA synthesis in response to IL-2. Similar events occurred during culture of DC with unmodified T cells (syngeneic MLR) but were quantitatively reduced. The experimental approach was to co-culture DC and T cells for up to 20 h and then kill the DC with specific antibody, or anti-Ia antibody, and complement. Subsequent proliferation was inhibited if the T cells were cultured in fresh medium. However, proliferation was restored when the lymphocytes were cultured in the original DC-T cell medium, or with a crude or a purified preparation of IL-2. IL-2 did not induce the proliferation of T cells that had been cultured in the absence of DC, and did not synergize with viable DC. We conclude that DC induce proliferation by tightly coordinating the release of, and responsiveness to, T cell growth factor or IL-2.

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“…It is well established that proliferation of at least some antigen-or mitogen-activated T cells is dependent on T-cell growth factors (TCGF) (16,17). Because TCGF are produced by Lyt-l cells (18), we tested if the enhancement of alloantigen-induced proliferation by aLyt-1 is related to production of TCGF.…”

mentioning

confidence: 99%

Effects of Lyt antibodies on T-cell functions: augmentation by anti-Lyt-1 as opposed to inhibition by anti-Lyt-2.

Hollander¹,

Pillemer²,

Weissman³

1981

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

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Monoclonal anti-Lyt-I (oiLyt-1) and aLyt-2 manifest inverse effects on allogeneic mixed lymphocyte reactions when added to the reaction mixtures without complement. aLyt-1 augments cell proliferation and generation of cytotoxic cells but has no effect on cell-mediated cytolysis, whereas aLyt-2 blocks cell proliferation, generation of killer cells, and cytolytic activity of killer cells. The augmenting effect of aLyt-I cannot be attributed to a direct mitogenic effect on T cells. Both inhibition by viLyt-2 and potentiation by aLyt-I require interaction of responder cells with the antibodies during the first 24 hr of the mixed lymphocyte reaction, indicating that early stages of the reaction are sensitive to Lyt antibodies. The enhancing effect of aLyt-I on alloantigeninduced T-cell proliferation is associated with augmented production of T-cell growth factors. When aLyt-I is present in mixed lymphocyte cultures, the supernatant media collected after 24 or 48 hr of culture induce higher proliferation of activated T cells compared to media of mixed lymphocyte cultures incubated in the absence of antibodies or in the presence of aLyt-2 which has no effect on secretion of growth factors. The differences in the effects of aLyt-1 and atLyt-2 could not be attributed to differences in heavy chain constant region functions because both were of the same Y2A immunoglobulin class and were used at the same concentration. The data suggest a possible role for Lyt-l molecules in early activation and mitogenesis processes such as production of growth factors.T lymphocytes mediate various immunological functions. They can be distinguished from other lymphoid cell populations by cell surface markers such as Thy-l. Lyt alloantigens (1-3) are useful markers for T-lymphocyte subpopulations because T cells with different functions can usually be distinguished on the basis of their Lyt phenotype. Thus, it has been widely accepted that helper cells and cells involved in delayed type hypersensitivity express the Lyt 1+2-3-phenotype, whereas killer cells and suppressor cells have the Lyt 1-2+3+ phenotype (4-6) and are derived from Lyt 1+2+3+ precursors (7-9). [In fact, Lyt 1 is expressed on most if not all Lyt 2+3+ cells; low to background levels are found on these cells (10), which here we call operationally Ly 1-2+3+. ] Although T-cell alloantigens have been extensively studied with regard to their inheritance, biochemistry, and selective expression on functionally distinct subsets (4-6, 11-15), it is not known whether these antigens play a role in the function ofT cells.We have recently found (10) that anti-Lyt-2 antibodies (aLyt-2), but not aLyt-1, blocked alloantigen-induced T-cell proliferation, as well as T-cell mediated cytolysis, in the absence of added complement. In contrast to antigen-induced stimulation, concanavalin A (Con A)-induced T-cell proliferation was not inhibited by aLyt-2 but was inhibited by aThy 1 (10). This led to the suggestion that aLyt-2 interfere with T-cell proliferation at the level of the T-cell a...

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Studies on T lymphocyte activation II. The target cells for concanavalin A‐induced growth factors

Cited by 137 publications

References 16 publications

Regulation of T cell autocrine growth. T4+ cells become refractory to interleukin 2.

Regulation of T cell autocrine growth. T4+ cells become refractory to interleukin 2.

Dendritic cells initiate a two-stage mechanism for T lymphocyte proliferation.

Effects of Lyt antibodies on T-cell functions: augmentation by anti-Lyt-1 as opposed to inhibition by anti-Lyt-2.

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