Holger Kirchner

Immunologic Reactivity of Lymphoid Cells in Tumors

There have been many studies of immune responses against tumors and almost all of these have focused on the reactivity in the blood or spleen. From such studies, it has become clear that a wide variety of effector cells and types of immune functions may be involved in antitumor responses. Particular attention has been directed toward T cells that may be directly cytotoxic against tumor cells or may proliferate or produce lymphokines upon stimulation with tumor antigens. However, other effector mechanisms may be involved and need to be considered. These include B cells, which can produce antibodies that affect tumor cells directly or that interact with K cells or macrophages and thereby mediate antibody-dependent cell-mediated cytotoxicity; macrophages and monocytes, which are spontaneously cytotoxic or can be activated to become cytotoxic against tumor cells; and natural killer (NK) cells, a subpopulation of lymphocytes with spontaneous cytotoxic reactivity against tumor cells.

Resistance of C3H/HeJ Mice to Lethal Challenge with Herpes Simplex Virus

Summary In vitro replication of herpes simplex virus (HSV) in murine spleen cells requires simultaneous cell stimulation with a B-cell mitogen such as lipopolysaccharide (LPS). As expected, spleen cells of LPS-unresponsive C3H/HeJ mice did not support HSV replication in LPS-pretreated cultures, while spleen cells from closely related but LPS-responsive C3HeB/FeJ did. More importantly, the C3H/HeJ strain was found to be intrinsically resistant to HSV infection in vivo. After intraperitoneal (ip) inoculation, HSV was 50-120 times more virulent for C3HeB/FeJ mice than for the C3H/HeJ strain. This resistance appeared to be due to a failure of HSV to replicate in C3H/HeJ peritoneal cells, since after ip infection with HSV, recovery of virus was higher and more consistent from peritoneal exudate cells of C3HeB/FeJ mice than from C3H/HeJ mice. In addition, no difference in lethality was observed between these two strains after a direct intracerebral inoculation of HSV. This observation that LPS-unresponsive mice are intrinsically resistant to lethal HSV infection, coupled with the LPS requirement for HSV replication in vitro, suggests an important but as yet unexplained link between host sensitivity to HSV and to LPS.