T-Lymphocyte precursors. I. Synergy between precursor and mature T lymphocytes in the response to concanavalin A.

Abstract

When mouse bone marrow cells are mixed with cortisol-resistant thymocytes and stimulated in vitro with concanavalin A, the mitogenic response observed is much greater than additive, that is, it is synergistic. Between 94 and 96% of responding cells could be identified as T cells (Thy-1 positive) and of these, 79-100% derived from the cortisol-resistant thymocyte population, not from the bone marrow. Purified macrophages could not replace bone marrow; and marrow depleted of mature T or B cells worked as well as normal marrow. Thus, T and B cells and macrophages were ruled out as the synergizing cell of bone marrow. Nude spleen contained 10 times as many precursors of T cells as did nude marrow and was 10 times better at synergy with cortisol-resistant thymocytes. This implication of the pre-T cell as synergizer was supported by the finding that the synergistic activity of marrow was lost on preincubation, but maintained if the preincubation medium contained thymosin or cyclic AMP. Thus, the ability to enhance the response of relatively mature T cells to Con A is a property of pre-T cells. It is anticipated that this property will allow more detailed studies of T-cell precursor development in mice, and possibly in man.

Quantitative Studies of the Activation of Cytotoxic Lymphocyte Precursor Cells

“…TTie evidence that population I gives rise to population II (Miller et al 1977) is indirect, and the two cells may yet prove to have independent origins. Another possibility is that population I cells are non-© bearing prethymic stem cells (Komuro & Boyse 1973, Cohen & Fairchild 1976 which somehow aid in the activation of CLP.…”

Different Requirements for T Cells Responding to Various Doses of Concanavalin A

“…14-16, 20, 27, 29, 31]. The helper cells have been characterized as macrophages [3,11,12,14,20,27,29], T cells [5,8,9] and B cells [3]. It has also been reported that low numbers of adherent cells can enhance the response to polyclonal T-cell activators, whereas higher numbers of adherent cells inhibit the T-cell response [10,18].…”

An in vitro assay for T lymphocyte progenitors (CFU‐preT)

“…They do, however, synergistically support the proliferation of a small number of mature T cells stimulated by Con A, as do pre-T cells [8] . One hundred thousand lymph node cells cultured alone gave a Con A response of 4,736 cpm; in the presence of 50,000 bone marrow cells this was 11,795 cpm, and in the presence of 50,000 colony cells, 16,892 cpm.…”

“…This synergistic interaction has been used as the basis of a T cell progenitor assay [8]. It was applied to pooled colony cells by mixing them with small numbers of syngeneic lymph node cells and assaying the increase in tritiated thymidine incorporation following Con A stimulation, as described elsewhere [8].…”