CELLULAR
IMMUNDLOGY
Heterogeneity
40, 58-68
(1978)
of Human
Natural
Killer
Cell
Populations1
Natural killing (NK) in human donors was determined hy the ability of peripheral blood subpopulations to lyse the mycloid target. K561, in a 2 to 4 hr “‘Cr release assay. The most active cell was a non-T cell I\-hich passed through nylon columns (representing 10 to 2570 of column passed cells). X second column passed cell population, with characteristics of T lymphocytes (75 to 90% of column passed cells), was also capable of mediating natural killing. Non-T cells which were retained by the nylon columns (45 to 5570 of adherent cells) lacked NK activity. However, nylon adherent T cells (45 to 55% of adherent cells) were consistently active in NK assays, illustrating an important subset of NK effector cell often overlooked. Both column passed and adherent T cells were further separated according to their ability to hind IgG or IgM immune complexes. showing that those mediating NK have receptors for IgG (T+y+) but not for Ighl (T,w+).
IXatural killing (NK)’ is non- a well recognized l~henomenon described in hmm~ (l-Z>, mouse (3-4), and rat systems (5-6). It can be defined as the reactivity of lymphoid cells against certain syngeneic (I), allogeneic (2-6) or xenogeneic (7) tumor cells in the absence of any apparent nntigenic stimulation. The possible significance of natural killing as a mechanism for ilnn~u~7osL~rveillance has generated much interest in the phenomenon and while the in z&o significance of NK in humans is not coml~letely understood there are several animal nmlel systems where tumor resistance (8-9) and bone marrow resistance (10) have been correlated to levels of NK. Considerable controversy has acconq~anietl the recent upsurge of interest in NK. One unresolved question is whether NK and antibody-dependent-cellular cytotoxicity (AAllCC) activities are mediated by the same or different cells. A related problem concerns the nature of the human effector cell(s). It is generally agreed that surface Ig positive I3 cells and macrophages are not effecters in SK. Several authors have identified as the most active SK cell a nomT cell (11, 12) with some acknowledging that a T cell may also contribute to natural killing (13). However, 1 Supported by USPHS Grant No. CA 14236 and USPHS-TG Grant No. CA 09058. 2 Abbreviations used in this paper : NK, natural killing ; ADCC, antibody-dependent-cellular cytotoxicity ; PBL, peripheral blood leukocytes ; PBS, phosphate buffered saline ; MEM, minimal essential medium ; Cp, nylon column passed ; SRC, sheep red blood ccl1 ; RBC, red blood cell ; EA, erythrocyte antibody complex ; and m$, macrophage.
0008-X749/78/0401-0058$02.00/0 Copyright All rights
0 1978 by Academic Press, Inc. of reproduction in any form reserved
~1.\'1‘1'I~1.\1.5
.\Sl)
~II:'fllol).c;
60
C‘omparison
KALL
of Hun~an
N K Activity
Effector!+
After
AND
KOREN
TARI-E
1
Ammonium
Chloride
Treatment
(z4C’K)
‘;]t it
tlumottticlwr
wlls
the
the
tliffrt-wccs.
l~lootl
nclll-T
\\.r
rt ~gatditig
have
3 1. c~thrrs
hantls.
\vvII.
selntxticm rtq)ortctl
]J;Lss”1
mxs
as cot~ltl
Ix3ipheral
;tttcl motiocytc~. jll~,)l~et] t]qJletic,ti
colrttllti,
thr
the
( 11-I our
fonvartl
authors
cells ;Iltllougll
?‘ crlls \vhich
es]Jlaitl
ittto
\\liile
t1011-‘I‘
dif&rwces
I);lrti:tI]y
11vl011
wljaratrtl
tlicw
rwcti\-c ccl1 as the most effcrtors ( 1-C. 24 ). lit
technical \\‘r
ant1
\v;i5
of
wll5
tlic
vic\vI)oitits natm-nl
Imsitive tltc tn;tin
\~OOl
the
bvhich
activity.
Sevctxl
Iluman
iti
iracticm
cells.
coltttiiti
0.K
Ii I(C‘. the
otic
tlics activities
cells
untf31
‘1‘ ). lion.evcr. If -1‘ cells 1~
ti~loti
activitic.b
rqx~rtc~l
Sitiiil;trl~~.
‘l‘T,SK
0s
.stc’]w
thcrc~forc~
2 that
]KN~~s.
tktectetl
cell
to isolate
\v:L:, .s:et aside
iii
the
sul~]~oIjttl:ttioti~.
Fiq.
‘I’,L--
‘I‘
cotiil~leses
atit1
;ilicIttot
IJC foutitl
I~wti
itiitiiutic
lg(;
coat~~l
srl~aratioii
a5 Itab
IgAl
nw
a~IIit7-rttt
attetii]~ttYl
7‘ wlls
aliquot
third
2 illustixtcs
glolntliti,
t1lrttt
A
(‘1)
Ig(;
nitli
Ix;\1 cati
thy
or
oiw
(‘1~ J‘ mid ;~dhcwtit
( Imth it1 the
littlc
:
‘L‘;/-.
I