T-T-cell interactions during the vitro cytotoxic allograft responses. I. Soluble products from activated Lyl+ T cells trigger autonomously antigen-primed Ly23+ T cells to cell proliferation and cytolytic activity.

Abstract

Secondary murine cytotoxic T lymphocyte responses from alloantigen-primed T cells can be induced in vitro by apparently unrelated regimens, such as addition of either concanavalin A (Con A), conditioned medium from Con A stimulated lymphocyte cultures, conditioned medium from secondary mixed lymphocyte cultures (MLC), or stimulator cells sharing only the I-region with the stimulating cells used for primary sensitization. We now report that upon polyclonal (Con A), or antigen-specific (MLC) stimulation, Lyl+ T cells release a factor, which in turn triggers alloantigen primed Ly23+ T cells to proliferation and cytolytic activity. The secondary cytotoxic T lymphocyte inducing factor (SCIF) is produced within 24 h. For its production, an intact protein metabolism, not DNA metabolism, is required. Once induced, the functional activity of SCIF is nonspecific and not H-2 restricted. SCIF allows exponential growth and long-term propagation of cytolytic Ly23+ T cells with specificity to alloantigens used for primary sensitization. SCIF induced activation of alloantigen primed Ly23+ T cells does not require the presence of alloantigens. The results therefore reveal a process by which Lyl+ T-cell-derived nonspecific factor(s) induce autonomously Ly23+ T-cell-mediated, antigen-specific, cytotoxic T lymphocyte responses.

Helper T cells for cytotoxic T lymphocytes need not be I region restricted

“…The involvement of soluble helper factors in CTL induction was suggested in several experiments that demonstrated the augmentation of suboptimal in vitro CTL responses by factors in supernatants from Sp Con A Sn or MLC supernatants (3,4,(27)(28)(29)(30)(31)(32). The absolute requirement of most cloned CTL for exogenous IL-2 (15,20,33) that is produced by T cells (34)(35)(36) argues that a discrete helper T cell is required and that at least one function of this cell is to provide IL-2 as well as possibly other soluble mediators to CTL.…”

“…Nonetheless, on the basis of mostly indirect results from a variety of experimental approaches, the most prevalent model of CTL activation is one that closely parallels models of B cell activation, i.e., that I regionrestricted helper T cells activated by interaction with antigen in the context of I region determinants deliver inducing signals to antigen-activated precursor CTL (1)(2)(3)(4)(5). In some models, the helper T cell interacts with CTL precursors via the restricted recognition of I region determinants expressed by the CTL precursor (1,2).…”

The induction of the human T‐cell growth factor receptor precedes the production of RNA and occurs in the presence of inhibitors of RNA synthesis

“…TCGF, a polypeptide growth hormone produced by the helper subset of T cells (27), performs a central function in the immune response. It not only supports the proliferation of TCGF-dependent cell lines, but it is obligatory in the T-cell proliferative response to antigens and to polyclonal activators (6,211.…”

Dissection of the proliferative and differentiative signals controlling murine cytotoxic T lymphocyte responses

“…Graded numbers of viable cells were incubated with a constant number (2 × 106) SlCr-labeled P815 tumor cells in the presence of 10/xg/ml PHA-P (Gibco Laboratories). Percent specific lysis was calculated as detailed previously (6).…”