Synergistic and suppressive interactions among mouse T lymphocytes in the response to phytohemagglutinin.

Abstract

A synergistic effect in the proliferative response to phytohemagglutinin (PHA) can be observed in cultures containing a mixture of mouse CBA/Ca lymph node cells (LNC) and syngeneic CBA/T6T6 thymocytes (ThC) when compared to cultures containing only one cell type. This effect was analyzed, at various days of culture and in LNC-ThC mixtures of different ratios, by comparing the origin of the cells in mitosis (detected by caryotypic analysis), the stimulation of DNA synthesis, the number of blasts, and the percentage of blasts labeled after pulses of [3H]thymidine (detected by autoradiography). The following conclusions were reached: (a) ThC are induced to proliferate by the presence of LNC, while they are almost unresponsive to PHA when cultured alone; and (b) the strongest "synergistic" effect is exerted on LNC, whose proliferation is markedly enhanced. Evidence is presented that this last effect is not specific to the presence of ThC, but results from a dilution of LNC which retards the time when the culture reaches a critical concentration of blasts, above which proliferation progressively stops. Thus, conditions of culture allowing the response to PHA of a low concentration of LNC leads to the most prolonged T-cell proliferation. These observations may be relevant to the types of T-cell interactions, "synergistic" or "suppressive," occurring during in vitro or in vivo immune responses.

Cellular Cooperation in Lymphocyte Activation

“…The latter notion is supported by our earlier observation that the T(VI) population was different from that of T(III) in that the former failed to cooperate with B cells [25]. This kind of T-T interaction may be related to the syner gistic interaction found between thymocytes and lymph node cells [34], or between ma ture and immature thymocytes in mice [35]. The fact that N-ALL, and even epidermal cells as well as B-ALL, displayed an en hancing activity similar to that of B(VIII) may be attributable to the possibility that any lymphoid and non-lymphoid cells ex cept autologous T cells alone may function as promoter cells in T-cell activation.…”

“…The binding of mitogen to the B-cell surface, making an effective stimu lant for T cells ('matrix presentation of mi togen' [34]), does not seem to be essential, since simple binding of mitogen to the mc-treated T-cell surface does not effec tuate enhanced T-cell response. Nonspecific facilitation with unresponsive cells or a feeder layer effect of B cells [31,34] may be responsible, while mc-treated, unrespon sive T cells alone failed to promote en hancement, indicating that cell-to-cell inter action between different antigenic determi nants is necessary as the second signal in this kind of physiological interaction. It ap pears that T-cell enhancement was induced by the T-cell recognition of the B-cell-specific determinants which were not present on T cells.…”

The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes. III. B-cell dependence for T-cell proliferation.

“…In studying the proliferative response to PHA by a mixture of lymph node cells and syngeneic thymocytes, Piquet et al (26) attributed the augmented response of the mixture to a nonspecific dilution of lymph node blasts. To determine whether this was also the case with LPF stimulation, and to provide information on the density of the accessory cells, adherent spleen cells were fractionated on a discontinuous BSA gradient (Table II).…”

“…T-T-cell interactions have been implicated in the proliferation of lymphocytes to Con A (27)(28)(29)(30) and PHA (26). However, the synergy between subpopulations of T cells in LPF-induced blastogenesis is improbable.…”

In vitro maturation of immature thymocytes into immunocompetent T cells in the absence of direct thymic influence

“…Induction of Proliferation of PNL + Thc in Culture. SUP of 24-h cultures Of Con A or PHA stimulated LN cells or spleen cells are known to stimulate the proliferation of Thc (20)(21)(22)(23)(24)(25)(26). When PNL + Thc were cultured with Con A in a medium supplemented with 30% of such a SUP, or in presence of lethally irradiated LN cells, a strong proliferative response was observed (Table II).…”