# IN VITRO INDUCTION OF NK CYTOTOXICITY

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 1990 · $170,495

## Abstract

Lymphocytes can be induced to mediate cytotoxic reactions against a variety
of target cells by in vitro manipulations.  These reactions can be against
either NK-sensitive target cells ("NK-like" or "anomalous" killing) or
against NK-resistant targets ("lymphokine activated killing").  Cytotoxic
reactivity can be induced with various stimuli including mixed lymphocyte
culture or interleukin-2 (IL-2).  These types of cytotoxicity bear a number
of similarities with natural killer (NK) cell mediated cytotoxicity,
although some features such as the spectrum of target cells killed are
quite different.  We propose to investigate the similarities between these
types of cellular cytotoxicity basing our studies on the hypothesis that
LAK and NK are of the same lineage, are regulated similarly, and recognize
the same target structures.  The ideal means to study the development of
these effector cells would allow for the induction of cytotoxicity from
non-cytotoxic precursors.  We have developed two such precursor systems;
the induction of cytotoxicity with IL-2 from naturally NK-inactive human
thymocytes and IL-2 stimulation of peripheral blood lymphocytes depleted of
NK cells with the toxic lysosomotropic drug L-leucine methyl ester.  The
phenotype of cells capable of developing cytotoxic reactivity, the sequence
of signals that must be delivered to these cells to develop cytotoxic
function, and the specificity of the induced cytotoxicity will be studied.
The effects of adherent cells and adherent cell products on the in vitro
development of cytotoxicity will be studied.  We have demonstrated the
existance of suppressor cells for NK effector function and for the
acquisition of the IL-2 and transferrin receptors.  These cells will be
characterized and their mode of action determined.  The specificity of LAK
and NK cells will be compared by immunoselection of target cells with LAK
or NK effector cells and comparing the sensitivity of the selected targets
to these effector systems.  By examining the similarities and differences
between LAK and NK at the precursor, regulatory, and effector levels we
expect to be able to determine the functional relationship between these
cell types.

## Key facts

- **NIH application ID:** 3172121
- **Project number:** 5R01CA034442-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **SAM.gov UEI:** RN64EPNH8JC6
- **Principal Investigator:** SIDNEY H GOLUB
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $170,495
- **Award type:** 5
- **Project period:** 1987-02-12 → 1992-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172121

## Citation

> US National Institutes of Health, RePORTER application 3172121, IN VITRO INDUCTION OF NK CYTOTOXICITY (5R01CA034442-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172121. Licensed CC0.

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