# TARGET CELL LYSIS BY CYTOLYTIC EFFECTOR CELLS

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 1990 · $132,568

## Abstract

Cytotoxic T cells (CTL) are one of the cornerstones of the immune
system.  There is therefore much interest in understanding the
mechanism by which they lyse targets, which is the overall goal of
this proposal.  Although significant strides have been made in our
understanding of CTL lysis many questions remain open.  Adsorption
of CTL to targets via receptors triggers polarization of
cytoskeletal elements in the CTL.  This leads to reorientation of
the Golgi apparatus (GA) towards the target binding site and
secretion of channel forming proteins -perforins (PF) - which are
thought to cause target cell lysis.  Recent evidence suggest s that
this sequence of events established with in vitro CTL clones does
not operate in vivo induced CTL.  Evidence is also accumulating
that target lysis by channel formation may not be the universal
mechanism of CTL lysis and that the target itself plays an active
role in its lysis.  We propose to explore several aspects of the
concurrent models for CTL lysis in in vivo induced CTL, because
they have not yet acquired abnormal properties in vitro.  CTL will
be highly purified and tested whether they show GA reorientation
when bound to targets because this reaction is thought to signal
proper target recognition.  Next CTL will be tested as to their
ability to insert PF channels into erythrocyte membranes.  To
induce this reaction we will use bifunctional anti-target anti-T
cell receptor antibody conjugates.  If CTL fail to insert channels
into erythrocytes we will test whether removal of nuclei from
targets inhibits target lysis.  In drug inhibition studies we will
examine whether continued lytic activity of the CTL on one hand and
lytic susceptibility of the target on the other require protein
synthesis prior to CTL-target binding.  Preliminary data support
the view that targets participate in CTL induced lysis.  To explore
how targets participate in lysis we propose several approaches, one
of which is based on the ability of protein synthesis inhibitors
to interfere with CTL lysis.  Another is based on the concomitant
occurrence of resistance to CTL lysis and resistance to
glucocorticoids in one cell line.  We propose to examine whether
there indeed exists a correlation between glucocorticoid resistance
and CTL sensitivity.  This would provide support for a common
pathway for both mechanisms of cell lysis.  We also propose to
select CTL resistant targets to explore whether they acquire
resistance to PF and/or glucocorticoids.  These variants will
provide the tool to study the postulated suicide pathway.  Finally,
we will explore whether in vivo induced CTL change their mode of
lysis upon prolonged culture in vitro and activate pathways of cell
mediated lysis that have been described for cloned CTL.

## Key facts

- **NIH application ID:** 3178838
- **Project number:** 5R01CA039623-05
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **SAM.gov UEI:** G88KLJR3KYT5
- **Principal Investigator:** GUNTHER DENNERT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $132,568
- **Award type:** 5
- **Project period:** 1985-07-01 → 1993-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178838

## Citation

> US National Institutes of Health, RePORTER application 3178838, TARGET CELL LYSIS BY CYTOLYTIC EFFECTOR CELLS (5R01CA039623-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178838. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*