Modulation of HIVGP120 Antigen-Specific Immune Responses In Vivo by Δ9-Tetrahydrocannabinol


Approximately 25 % of HIV patients use marijuana for its putative therapeutic benefit; however, it is unknown how cannabinoids affect the immune status of HIV patients. Previously, a surrogate in vitro mouse model was established, which induced CD8+ T cell proliferation and gp120-specific IFNγ production. ∆9-Tetrahydrocannabinol (THC), the predominant psychoactive compound in marijuana, suppressed or enhanced the responses depending on the magnitude of cellular activation. The purpose of the current study was to investigate whether THC produced similar effects in vivo and therefore a mouse model to induce HIVgp120-specific immune responses was established. A gp120-expressing plasmid, pVRCgp120, or a vector plasmid, pVRC2000, was injected intramuscularly into mice, which were also dosed with THC orally. The gp120-specific IFNγ and IL-2 responses were detected when splenocytes were restimulated with gp120-derived peptide 81 (IIGDIRQAHCNISRA), which was identified as being immunodominant. Various cellular populations were activated in response to pVRCgp120 stimulation followed by peptide restimulation, as evidenced by increased expression levels of activation markers (e.g., CD69, CD80, and major histocompatibility complex II [MHC II]). The IFNγ response and cellular activation were enhanced by THC in C57Bl/6 wild type (WT) mice but suppressed or not affected by THC in cannabinoid receptor 1 (CB1) and 2 (CB2) knockout (CB1 −/−CB2 −/−) mice. Furthermore, CB1 −/−CB2 −/− mice exhibited augmented IFNγ production when compared to WT mice in the absence of THC. Collectively, our findings demonstrate that under certain conditions, THC enhances HIV antigen-specific immune responses, which occurs through CB1/CB2-dependent and -independent mechanisms.

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Adenylyl cyclase


Activator protein-1


Antigen presenting cell


Bovine calf serum


Cyclic adenosine 3′,5′-monophosphate

CB1 :

Cannabinoid receptor 1

CB2 :

Cannabinoid receptor 2

CB1 −/−CB2 −/− :

CB1 and CB2 null


Corn oil


Cytotoxic T lymphocytes


Dendritic cell


Dimethyl sulfoxide


Fragment cystallizable receptors


G protein-coupled receptor



KV :

Voltage-gated potassium channels


Monocyte chemotactic protein-1


Mean fluorescence intensity




Nuclear factor of activated T cells


Nuclear factor kappa-light-chain-enhancer of activated B cells


No treatment


Phosphate buffered saline


Simian immunodeficiency virus




Transient receptor potential




Wild type


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The authors thank Jose Suarez and Natalia Kovalova for technical support during the study, and Kimberly Hambleton for assistance with submission of the manuscript.


This study was funded by National Institutes of Health (grant number DA007908).

Conflict of Interests

The authors declare that they have no conflict of interest.

Authorship Contributions

• W Chen, BLF Kaplan, and NE Kaminski participated in research design

• W Chen and RB Crawford conducted experiments

• W Chen performed data analysis

• W Chen wrote the paper

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Correspondence to Norbert E. Kaminski.

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Chen, W., Crawford, R.B., Kaplan, B.L.F. et al. Modulation of HIVGP120 Antigen-Specific Immune Responses In Vivo by Δ9-Tetrahydrocannabinol. J Neuroimmune Pharmacol 10, 344–355 (2015).

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  • Cannabinoids
  • Cannabinoid receptors
  • HIVgp120
  • Immune modulation