A virus specific cytotoxic thymus (T)-derived lymphocyte (CTL) response is composed of two major components; 1) an afferent (inductive) phase where antigen triggered CTL precursors (CTL-P) clonally expand and differentiate into effector cells and 2) an efferent phase where effector function (cytotoxicity) presumably mediates a protective role for the virus-infected host. At the effector cell stage, lytic activity is triggered following T cell receptor binding of extrinsic (viral) antigen. However, this event is deceptively complex and the sequelae leading to the expression of lytic activity remain obscure. Therefore, my first objective is to address two questions concerning events which are thought to be important in triggering anti-viral CTL activity; namely, 1) is insertion of viral antigens into the target cell plasma membrane an obligatory step in the generation of CTL target antigens and 2) are viral and H-2 antigens co-capped during CTL/target interaction? My second objective will focus on identifying and characterizing T cell derived inductive signals required for the generation of anti-viral CTL responses in vitro. More specifically, I will characterize T cell signals (both helper and suppressor) triggered during an anti-viral CTL response as well as test the hypothesis that memory CTLs possess a different maturational pathway than CTL-P. Both responder and nonresponder mouse strains will be evaluated in order to gain insights into the cellular basis of nonresponsiveness. The proposed studies will be performed using a simple, antigenically well defined virus system, vesicular stomatitis virus (VSV).
| Ciavarra, R P; Burgess, D H (1988) Antigen-presenting B cells: efficient uptake and presentation by activated B cells for induction of cytotoxic T lymphocytes against vesicular stomatitis virus. Cell Immunol 114:27-40 |
| Ciavarra, R P; Silvester, S; Brody, T (1987) Analysis of T-cell subset proliferation at afebrile and febrile temperatures: differential response of Lyt-1+23- lymphocytes to hyperthermia following mitogen and antigen stimulation and its functional consequence on development of cytotoxic lymphocytes. Cell Immunol 107:293-306 |
