Doctoral Dissertations

Date of Award

6-1985

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Microbiology

Major Professor

Barry T. Rouse

Committee Members

Richard J. Courtney, Arthur Brown, Alex Osmand, Robert N. Moore

Abstract

Evidence for a suppressor cell circuit regulating herpes simplex virus (HSV) specific cytotoxic T lymphocyte (CTL) induction is presented. Thus the stimulation of HSV immune murine splenocytes with HSV antigens results in the induction of suppressor cells which inhibit both HSV-specific CTL induction and lymphoproliferation. Through the use of coculture experiments it was possible to identify a radioresistant, Thy 1+, Lyt 2+, T cell responsible for the suppression. The induction of this cell required the participation of several distinct splenocyte populations. Thus Lyt 1+ and Lyt 2+ T cells as well as I-E+, I-J+ antigen presenting cells (APC) were required for the induction of the Lyt 2+ suppressor cell. Only the Lyt 2+ cell had to come from HSV-immune mice, both the Lyt 1 cells and the APC required for suppressor cell induction could be provided by HSV naive mice. In addition to the cellular requirement for suppression, several soluble factors were involved in the suppression. These factors were present in the supernatant fluids from HSV-stimulated, HSV-immune splenocyte cultures. Separation of the suppressive supernatant by gel filtration chromatography identified both non-specific and antigen-specific suppressor activities. The specific suppressor activity exhibited both antigen-specificity and genetic restriction in its action. Western blotting analysis of the specific suppressor activity indicated that it was both I-J+ and anti-idiotypic. Production of the suppressor factors required Lyt 2+ splenocytes. The ultimate suppression mediated by the specific factor was non-specific in its action and required the participation of a HSV-primed Lyt 1+ cell. A model is thus presented which describes the regulation of HSV-specific immune responses by a suppressor cell circuit which is specifically induced, but which mediates its activity non-specifically.

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