PMID- 1967264
OWN - NLM
STAT- MEDLINE
DCOM- 19900209
LR  - 20141120
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 144
IP  - 1
DP  - 1990 Jan 1
TI  - Expression of two distinct cytolytic mechanisms among murine CD4 subsets.
PG  - 23-31
AB  - A TNF (TNF-alpha and TNF-beta)-sensitive target, L929, and two TNF-resistant 
      targets, P815 and LK were used to compare the cytolytic activity among subsets of 
      CD4+ (Th) clones. Cytolytic activity was induced with either Con A, CD3-mAb, or 
      Ag-pulsed LK cells. Six Th1 clones are strongly cytolytic against all three 
      targets. In contrast, Th2 clones are either noncytolytic or weakly cytolytic. 
      Although there is an apparent correlation between TNF production, killing of L929 
      cells, and the killing of TNF-resistant targets, an anti-TNF serum (capable of 
      neutralizing both TNF-alpha and TNF-beta) selectively inhibits CD4 clones to lyse 
      L929 cells, whereas the lysis of P815 or LK cells was unaffected. The continuous 
      presence of noncytotoxic levels of Actinomycin D (AcD) and cycloheximide, but not 
      mitomycin C, cyclosporin A (CsA), or cholera toxin (ChT) inhibits the lysis of 
      Ag-pulsed, Ia-bearing LK cells; indicating a requirement for de novo synthesis of 
      RNA and protein for cytolytic activity. Although pretreatment with AcD, CsA, or 
      ChT strongly inhibits production of IL-2, TNF and IFN-gamma, only clones 
      pretreated with AcD lose cytolytic activity against Ag-pulsed, Ia-bearing LK 
      cells. These observations support a model of TNF-independent killing of 
      TNF-resistant targets. The TNF-independent cytolytic activity does not correlate 
      with serine esterase activity released into media upon activation of CD4 clones. 
      Moreover, the effects of metabolic inhibitors on serine esterase release do not 
      correlate with their effects on cytolytic activity. Collectively, the data 
      demonstrate that activated CD4 cells express two distinct cytolytic activities; a 
      TNF (and IFN-gamma)-mediated cytotoxicity and a TNF (and IFN-gamma)-independent 
      cytolytic activity. Both pathways require de novo synthesis of RNA and protein 
      and appear to be independent of granule enzyme release. Only the TNF-independent 
      cytolytic activity is resistant to CsA and ChT inhibition.
FAU - Ju, S T
AU  - Ju ST
AD  - Arthritis Center, Boston University School of Medicine, MA 02118.
FAU - Ruddle, N H
AU  - Ruddle NH
FAU - Strack, P
AU  - Strack P
FAU - Dorf, M E
AU  - Dorf ME
FAU - DeKruyff, R H
AU  - DeKruyff RH
LA  - eng
GR  - AI-24571/AI/NIAID NIH HHS/United States
GR  - CA-39790/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Cyclosporins)
RN  - 0 (Lymphokines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9012-63-9 (Cholera Toxin)
RN  - EC 3.1.- (Esterases)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cholera Toxin/pharmacology
MH  - Clone Cells
MH  - Cyclosporins/pharmacology
MH  - *Cytotoxicity, Immunologic
MH  - Esterases/metabolism
MH  - Immunity, Cellular
MH  - In Vitro Techniques
MH  - Lymphokines/biosynthesis
MH  - Mice
MH  - Neutralization Tests
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - T-Lymphocytes, Helper-Inducer/immunology
MH  - Tumor Necrosis Factor-alpha/*physiology
EDAT- 1990/01/01 00:00
MHDA- 1990/01/01 00:01
CRDT- 1990/01/01 00:00
PHST- 1990/01/01 00:00 [pubmed]
PHST- 1990/01/01 00:01 [medline]
PHST- 1990/01/01 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1990 Jan 1;144(1):23-31.