Limiting dilution analysis of T cells suppressing the primary antibody response to sheep erythrocytes.

The immune system is often seen as an organ whose primary function is discriminating between "self" and "nonself." Theoretically, there are several possible ways it can exert such a function. Earlier, it has been discussed that clones with receptors recognizing "self-determinants" are deleted during ontogeny. However, it is now well established that the normal adult repertoire does contain T and B cells with anti-self specificity. Nevertheless, in most cases autoimmune reactions are avoided, either due to lack of stimulation or due to active control mechanisms like suppression. There are various types of suppression described in the literature, ranging from highly specific to totally nonspecific suppression. A very attractive and universal form of suppression was proposed by Jerne in his network hypothesis: in the nonimmune state, cells of the immune system communicate with each other via interactions of their specific receptors and thus form a self-suppressive network. This paper describes the attempt to estimate frequencies of suppressor T (Ts) cells existing in the normal nonimmunized mouse. Ts cells are defined functionally in a suppressor assay, i.e., by suppression of the in vitro primary immune response of spleen cells to sheep erythrocytes. The experimental procedure involves limiting dilution of T cells into the suppressor assay followed by a quantitative analysis of the antibody responses (PFC assay or ELISA) and Poisson statistics. Several separate "peaks" of suppression are observed, depending on the number of T cells in the assay. Varying from experiment to experiment, these peaks reach maxima of suppression ranging from 20 to 80%. Low numbers of T cells are especially efficient in suppression, being themselves counterregulated at higher cell numbers. With increasing T cell numbers, suppression will appear and disappear again several times--a phenomenon already described by us for other functional T cell populations [reviewed in Eichmann et al. (1983): Springer's Sem. Immunopathol. 6:7].(ABSTRACT TRUNCATED AT 400 WORDS)