MOPC-315 is an anti-TNP IgA-secreting BALB/c plasmacytoma which is composed of lymphocytoid, non-secretory cells, IgA 315- secreting plasmacytoid cells, and intermediate cells. During in vivo growth the lymphocytoid, non-secretory 315 cells proliferate and differentiate into the IgA 315-secreting plasmacytoid cells. That growth and differentiation can be regulated in vivo and in vitro by carrier-specific helper, suppressor, and contrasuppressor T cells. Some of the differentiation regulating T cells specifically recognize not only carrier antigen but also IgA 315 idiotopes. The experiments described herein involve production and characterization of monoclonal T cell lines from sheep erythrocyte (SRBC)-immune BALB/c mice which can enhance, suppress, or contrasuppress the growth or secretory differentiation of MOPC-315 cells in vitro. Since in vivo and in vitro experiments suggest that regulation is occurring due to T cell release of soluble regulatory factors, this grant also is focused on purification, and biochemical and serological characterization of the regulatory factors. This is particularly important since all of the regulatory cells appear to act on the non-secretory lymphocytoid population of MOPC-315 and appear to interact with the cells through either surface IgA 315 idiotopes or through surface IgA 315 binding TNP-SRBC. Thus, information about structure-function relationships of these factors is possible to obtain. Idiotype 315-specific differentiation helper T (THd) cell, SRBC-specific differentiation suppressor T (Tsd) cell, and idiotype 315-specific differentiation contrasuppressor T (TCSd) cell monoclonal lines have already been produced. Polyclonal THd cells can protect mice against MOPC-315 tumor growth by apparently reducing the cells proliferative potential by inducing its differentiation. Experiments designed to determine the mechanism by which THd cells can inhibit tumor progression in mice and efficacy of using purified idiotype 315- and SRBC- specific THd helper factors as therapeutic drugs against MOPC- 315 cells in vivo are described herein. These experiments may demonstrate that regulatory stimuli as well as cytotoxic intervention can have therapeutic effects on some tumors' progression.
| Rohrer, J W; Kemp, J D (1988) Function and regulation of SRBC-induced contrasuppressor T cells which modulate suppression of MOPC-315 cell secretory differentiation in vivo and in vitro. Immunol Res 7:45-55 |
