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Perinatal exposure to Δ9-tetrahydrocannabinol triggers profound defects in T cell differentiation and function in fetal and postnatal stages of life, including decreased responsiveness to HIV antigens.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2011 Nov; Vol. 339 (2), pp. 607-17. Date of Electronic Publication: 2011 Aug 10. - Publication Year :
- 2011
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Abstract
- Marijuana abuse is very prominent among pregnant women. Although marijuana cannabinoids have been shown to exert immunosuppression in adults, virtually nothing is known about the effects of marijuana use during pregnancy on the developing immune system of the fetus and during postnatal life. We noted that murine fetal thymus expressed high levels of the cannabinoid receptors CB1 and CB2. Moreover, perinatal exposure to Δ(9)-tetrahydrocannabinol (THC) had a profound effect on the fetus as evidenced by a decrease in thymic cellularity on gestational days 16, 17, and 18 and postgestational day 1 and marked alterations in T cell subpopulations. These outcomes were reversed by CB1/CB2 antagonists, suggesting that THC-mediated these effects through cannabinoid receptors. Thymic atrophy induced in the fetus correlated with caspase-dependent apoptosis in thymocytes. Thymic atrophy was the result of direct action of THC and not based on maternal factors inasmuch as THC was able to induce T cell apoptosis in vitro in fetal thymic organ cultures. It is noteworthy that perinatal exposure to THC also had a profound effect on the immune response during postnatal life. Peripheral T cells from such mice showed decreased proliferative response to T cell mitogen as well as both T cell and antibody response to HIV-1 p17/p24/gp120 antigens. Together, our data demonstrate for the first time that perinatal exposure to THC triggers profound T cell dysfunction, thereby suggesting that the offspring of marijuana abusers who have been exposed to THC in utero may be at a higher risk of exhibiting immune dysfunction and contracting infectious diseases including HIV.
- Subjects :
- Animals
Apoptosis drug effects
Apoptosis immunology
Cannabinoid Receptor Agonists
Cannabinoid Receptor Antagonists
Caspases metabolism
Dronabinol pharmacology
Female
Fetus drug effects
HIV Antibodies biosynthesis
HIV-1 immunology
Indoles immunology
Indoles pharmacology
Lymphocyte Activation
Lymphopoiesis drug effects
Mice
Mice, Inbred C57BL
Piperidines immunology
Piperidines pharmacology
Pregnancy
Psychotropic Drugs pharmacology
Pyrazoles immunology
Pyrazoles pharmacology
Receptors, Cannabinoid genetics
Receptors, Cannabinoid metabolism
Rimonabant
T-Lymphocytes drug effects
Thymocytes cytology
Thymocytes immunology
Thymus Gland embryology
Dronabinol adverse effects
Fetus immunology
HIV Antigens immunology
Marijuana Smoking adverse effects
Prenatal Exposure Delayed Effects
Psychotropic Drugs adverse effects
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0103
- Volume :
- 339
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 21831965
- Full Text :
- https://doi.org/10.1124/jpet.111.181206