T Cell-dependent Mediator in the Immune Response

Mechanism of T-cell help in the immune response to soluble protein antigens. I. Evidence for in situ generation and action of T-cell-replacing factor during the anamnestic response to dinitrophenyl keyhole limpet hemocyanin in vitro.

“…These data are also in agreement with reports on the production of TRF-like supernates upon stimulation of T cells educated to KLH (7,10,13) or heterologous erythrocytes (7,9) with the respective antigens. Our data demonstrate, furthermore, the ability of such a mediator induced by antigen to restore the immune response to a soluble protein antigen and show the presence and action of this factor in untreated spleen cell cultures from immunized mice without the addition of educated T cells.…”

“…Table I shows three independent experiments in which DNPKLH-primed and boosted spleen cells were stimulated in vitro by the combined addition of 1 /~g KLH and 0.1 ~g DNPBGG or DNPOVA. These findings are most easily explained by assuming the action of a nonantigen-specific mediator (TRF) (15), which is produced by the KLH-primed T cells (7,10,13) upon the reaction with KLH and which helps the DNPBGG or DNPOVA-stimulated B cells in the production of anti-DNP antibodies. A similar effect has been described by Hartmann (17) in the primary reaction of B cells to heterologous erythrocytes in vitro, and the reconstitution of the anti-SRBC reaction of T-cell-deprived spleen cells by TRF or similar nonspecific T-cell factors is well established (4,(8)(9)(10)(11)(12)(13)(14)(15), both in the primary and in the secondary (16) in vitro responses.…”

“…In vitro studies have shown that T-cell-replacing factor (TRF),I a nonantigen-specific mediator produced by activated T cells (15), can replace T cells in primary and secondary immune responses to heterologous erythrocytes (15,16). The action of TRF and similar factors described by other authors (4,(7)(8)(9)(10)(11)(12)(13)(14) has so far been demonstrated by restoring the immune response to heterologous erythrocytes in T-cell-deprived cultures by addition of preparations containing the factor. On the other hand, the experiments reported by Hartmann (17) have shown that T cells activated to erythrocyte antigens in vivo do, upon antigenic challenge in vitro, not only restore the response of B-cell cultures to the epitopes of the same erythrocytes, but also to those of erythrocytes from another species added simultaneously to the same cultures.…”

“…Under this assumption, several concepts have been developed to explain the nature of T-cell help itself. Among these are: the focussing of antigen by the T cell onto the B cell (2,3), a membrane interaction between the two cells (4), and the production of mediators, antigen specific (5-7) or nonspecific (4,(7)(8)(9)(10)(11)(12)(13)(14), by the antigen-stimulated T cell. In vitro studies have shown that T-cell-replacing factor (TRF),I a nonantigen-specific mediator produced by activated T cells (15), can replace T cells in primary and secondary immune responses to heterologous erythrocytes (15,16).…”

T-cell-dependent B-cell stimulation is H-2 restricted and antigen dependent only at the resting B-cell level.

“…This leads to activation of the helper T cells and to production of helper factor(s) by either the activated helper T cells or the macrophages (2,3). Clones of helper T cells require the presence of both the antigen and immune response (I) region-compatible macrophaiges to produce help for bone marrow-derived (B) cell stimulation (4).…”