Transduction of Effector-Suppressor T Cells by an Antigen-Specific Suppressor T Cell Factor and Lyt-1⁺,2⁺,3⁺ T Cells

Abstract

The cellular consequences in the suppression of IgG antibody formation initiated by an antigen-specific suppressor T cell factor (TsF) were investigated. The initial step of the suppression is the production of TsF by Lyt-2⁺,3⁺ T cells (Tsi) which activates Lyt-1⁺,2⁺,3⁺ acceptor T cells in the nylon wool-adherent T cell population. The activated Lyt-1⁺,2⁺,3⁺ T cells further generate a new effector-suppressor T cell (Tse) that belongs to the Lyt-2⁺,3⁺ T cell subset in the culture of nylon-adherent T cells with antigen. The Tse thus induced directly suppresses the responses mounted by B cells and nylon column-purified helper T cells in the absence of TsF. The origin of Tse was further examined by utilizing Lyt congeneic mice. The result indicates that Lyt-1⁺,2⁺,3⁺ acceptor T cells themselves do not differentiate into Lyt-2⁺,3⁺ Tse with losing Lyt-1 phenotype but facilitate the transduction of Tse from a preexisting precursor pool. These cellular interactions strongly suggest that Lyt-1⁺,2⁺,3⁺ T cells play a decisive role in an amplification of immunoregulation.

Regulation of Allotype-Linked NP^b Idiotype by an Idiotype-Positive Soluble Factor Derived from a T Cell Hybridoma

“…Thus, once Id+ I-J" Ts cells are acti vated, they could act on anti-idiotypic T cells or I-J recognizing T cells. Our previous study [4] determined the I-J-restricted 'transduction' process, while in this report we extended our observation to the anti-idiotypic Lyt-l+2+3+ 'transducer' T cells. This Id-restricted pathways should parallel with the carrier-specific 'transduction' by TsF with I-J restriction in the gene ration of final suppressor effector.…”

“…The majority of the response suppressed by TsF was NPb idiotype positive. This allotype-res tricted suppression gives a clear distinction from the previously reported pathway of the carrier-specific suppression in that TsF was capable of suppressing the responses mounted only by I-J compatible spleen cells regardless of the Igh-allotype [24], Carrier-spe cific TsF was found to activate an intermediary T cell of Lyt-T2+3+ phenotype to 'transduce' the final effec tor suppressor T cells only when TsF and transducer T cells share the same I-J but not Igh genotypes [4], The present study indicates that the IgVH-restricted suppression of NPb idiotype also requires the pres ence of an Lyt-1+2+3+ 'transducer'T cells to convey the effect of NPb-TsF. Such transducer cells are naturally present in strains with Ighb allotype regardless of their H-2 haplotypes.…”

“…It has not been deter mined whether or not these cells directly differentiate into the suppressor effector T cells or not. A previous publication from our laboratory, however, demon strated that in the carrier-specific suppression MHCrestricted TsF acts on Lyt-l+2+3+ 'transducer' to acti vate a process where suppressor effector T cells differ entiate from the pool of Lyt-1"2+ precursor cells [4], This process is also operative in the present experi mental system where NPh-TsF and responding cells share only H-2 but not IgVn as in the case of the sup pression of C3H antibody response. If NPb-TsF and responding cells do not share either H-2 or IgV(1, no suppression was achieved indicating that either res tricted pathway is necessary for the NPb-TsF-mediated suppression.…”

“…The other concept termed immunological circuit deals with sequential activation of different cell types which are not necessarily antigen-specific but are restricted by other components such as genes in the major his tocompatibility complex (MHC) [reviewed in 2,3]. A complex MHC-restricted pathway of the 'transduc tion' of the suppressor function through the activa tion of a specialized intermediary cell type has been reported in our previous publication [4], Although both regulatory pathways can be initiated by the same antigenic stimulation, no critical comparisons have been made between the experimental conditions which support apparently separate concepts. This dis tinction was, however, recently called into question by the fact that even in a typical circuit type regula tion, where functionally different subsets of T cells are sequentially activated to suppress the immune re sponse, Id-anti-Id interaction is one of the major re stricting elements in conveying the signal from one cell type to the other.…”

Structural analysis of antigen-specific Ia-bearing regulatory T-cell factors: gel electrophoretic analysis of the antigen-specific augmenting T -cell factor.

“…The absorption studies with immunoadsorbents of antigen and antibodies revealed that the intact TaF is a heterodimer of two discrete polypeptide chains, one carrying a determinant detectable by a monoclonal anti-Tindd directed to an Igh-1-linked allotypic structure of T cells and being associated with the antigen-binding site and the other expressing a unique determinant controlled by the I-A subregion of murine H-2 major histocompatibility complex but being different from known class II polypeptide chains. The antigen-binding polypeptide has an isoelectric point of pH 5.6, and the I-A polypeptide has an isoelectric point of pH 6.3. Two types of antigen-specific T-cell factors, one able to suppress (TsF) and the other able to augment (TaF) the antibody response, have been reported from our laboratory (1)(2)(3). These factors share certain interesting immunological characteristics and are considered to play important roles in the regulation of the immune response (reviewed in ref.…”