Marijuana components suppress induction and cytolytic function of murine cytotoxic T cells in vitro and in vivo

T. W. Klein, Yutaka Kawakami, C. Newton, H. Friedman

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Killer lymphocytes play a major role in host defense against tumors and infectious diseases. Previously, we reported that delta-9-tetrahydrocannabinol (THC) and Il-hydroxy-delta-9-tetrahydrocannabinol (Il-hydroxy-THC) suppressed the cytolytic activity of cultured natural killer (NK) cells. Also, we showed that the drugs appeared to be affecting a stage in the killing process subsequent to the binding of the killer cell to the target cell. In the present report, we have extended these studies to an examination of the effect of cannabinoids on the activity of cytotoxic T lymphocytes (CTLs). The cytolytic activity of CTLs generated by cocultivation with either allospecific stimulators or TNP-modified-self stimulators were suppressed by both THC and Il-hydroxy-THC treatment. Allospecific CTLs generated in vivo were also inhibited by an in vitro exposure to either THC or Il-hydroxy-THC, and the sensitivity of these cells to drug effects appeared to be greater than the sensitivity of the in vitro generated CTLs. Suppression of cytolytic function by THC and Il-hydroxy-THC ws maximal after a 4-h drug treatment, suggesting that the drug effects were inducible and therefore required a finite period of time to develop maximally. As seen in previous studies involving NK cells, drug treatment of mature CTLs appears to have little effect on the binding capacity of these cells for the target. However, the maximal killing capacity of the cells and the frequency of CTLs were significantly reduced by drug treatment. In addition to suppressing the cytolytic activity of mature effector CTLs, we also show that drug treatment inhibits both the proliferation of lymphocytes responding to an allogeneic stimulus and the maturation of these lymphocytes to mature CTLs. Similarly, CTL activity developing in vivo could be inhibited by THC injection. These results suggest that CTLs are inhibited by cannabinoids by at least two mechanisms. First, the cytolytic activity of mature killers is suppressed at some point beyond the binding to the target cell. Second, the cannabinoids appear to suppress the normal development of these mature effector cells from less mature precursor cells.

Original languageEnglish
Pages (from-to)465-477
Number of pages13
JournalJournal of Toxicology and Environmental Health
Volume32
Issue number4
Publication statusPublished - 1991
Externally publishedYes

Fingerprint

T-cells
Dronabinol
Cytotoxic T-Lymphocytes
Cannabis
T-Lymphocytes
Drug therapy
Lymphocytes
Cannabinoids
Pharmaceutical Preparations
Natural Killer Cells
In Vitro Techniques
Therapeutics
Coculture Techniques
Communicable Diseases
Tumors
Cultured Cells
Injections

ASJC Scopus subject areas

  • Toxicology
  • Pollution

Cite this

Marijuana components suppress induction and cytolytic function of murine cytotoxic T cells in vitro and in vivo. / Klein, T. W.; Kawakami, Yutaka; Newton, C.; Friedman, H.

In: Journal of Toxicology and Environmental Health, Vol. 32, No. 4, 1991, p. 465-477.

Research output: Contribution to journalArticle

Klein, T. W. ; Kawakami, Yutaka ; Newton, C. ; Friedman, H. / Marijuana components suppress induction and cytolytic function of murine cytotoxic T cells in vitro and in vivo. In: Journal of Toxicology and Environmental Health. 1991 ; Vol. 32, No. 4. pp. 465-477.
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