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The syngeneic t t lymphocyte reaction i. induction of primary t anti t cell proliferative responses in t cell cultures stimulated with self and antigen reactive t cells



The syngeneic t t lymphocyte reaction i. induction of primary t anti t cell proliferative responses in t cell cultures stimulated with self and antigen reactive t cells



JMCI (Journal of Molecular and Cellular Immunology) 2(6): 331-342



The generally accepted "Gershonian" view of immunoregulation attributes T cell-mediated regulation of immune responses to the activities of discrete T cell subsets with specialized functions such as help, suppression, and contrasuppression. Several observations made in our laboratory are not compatible with this paradigm. For instance, careful quantitations of carrier-specific T cell help to hapten-specific B cells in an adoptive transfer system yielded complex dose-response curves that could not be explained on the basis of interactions between discrete subsets of helper and suppressor cells. Rather, the results were most easily interpreted according to a model based on the following assumptions: (1) Regulation of helper T cell activity is a dose-dependent, dynamic property of T cell populations that exhibit a high degree of connectivity (self-recognition) and (2) helper T cells have the ability to perform different functions, depending on the current activity of other interacting lymphocytes. A good example of cloned T cells capable of performing multiple immunoregulatory functions was provided by the IEk-specific self-reactive Lbd line which provided help, suppression, and contrasuppression to T cell dependent PFC responses (see Quintans et al., 1986). Since these effects were strictly dependent on the levels of antigen-specific T cell help, we hypothesized that Lbd cells interacted with other T cells to modulate their function. In this paper, we directly test the hypothesis that activated T cells can interact directly with resting T cells and describe the proliferative component of a syngeneic T cell anti-T cell response induced by antigen and self-reactive helper and cytotoxic T cells. In a follow-up report, we will describe the effector component of the T anti-T cell response. In this paper, we show that (1) Lbd cells and other autoreactive T cell lines induce a primary proliferative response in cultures of syngeneic T cells; (2) the capacity to stimulate syngeneic T cell proliferation is shared by FGG and KLH-reactive T cells; (3) the T anti-T cell response occurs in cultures depleted of Ia-bearing cells and it is susceptible to inhibition by anti-Ia antibodies; (4) T cells also proliferate to T cells stimulated with Lbd or antigen-reactive T cell lines, and thus propagate a chain of T anti-T cell reactions; (5) second-order T anti-T reactions are also inhibitable by GK1.5 (anti-L3T4) and anti-Ia antibodies, but the inhibitions lack the fine specificity of those found in primary T anti-T reactions; (6) both L3T4+ and Lyt2+ T cells can mount an anti-Lbd responses; and (7) an Lyt2+ cloned anti-Lbd cytotoxic line can also induce a GK1.5 inhibitable T anti-T cell response. Our findings demonstrate the existence of a highly connected T cell network and provide a rationale to study the population dynamics of T-T cell interactions and their immunoregulatory consequences.

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