title: The use of growth factors to modulate the activities of antigen-specific CD8+ T cells in vitro.
abstract: BACKGROUND
  Adoptive T cell therapy depends on the harvesting of the cells from the host, their activation in vitro, and their infusion back to the same host. The way of activating the T cells in vitro is a critical factor for their homing, survival and function in vivo. Sustaining T cell homing molecules, particularly CD62L, is benefic for the trafficking of the adoptive transferred cells.
  
  
  OBJECTIVE
  The aim of the present study is to test whether insulin-like growth factor-1 (IGF-1), thymosin- α1 (T-α1) as well as all-trans retinoid acid (ATRA) alone or in combination with IL-2, IL-12, IL-15 can enhance the activation and survival phenotypes of antigen-activated T cells in vitro.
  
  
  RESULTS
  To this end, OT-1 transgenic T cells were used as a model. These CD8+ T cells recognize OVA peptide presented by MHC class-I. The results showed that antigen stimulation of OT1 cells resulted in their activation as evidenced by the decrease in surface expression of CD62L, analyzed for 3 days after antigen stimulation and was more pronounced on day 5. The addition of IL-12 or IGF-1 alone but not of IL-2, IL-15 augmented OT-1 cell activation measured on day 5. Interestingly, the combination of IL-12 with IGF-1 sustained the expression of CD62L on OT1 cells. Although the addition of ATRA alone or in combination with IL-12 resulted in decreases in CD62L expression on day 3, they showed a dose-dependent effect on the restoration of CD62L expression on day 5. The analysis of the activation-induced cell death (apoptosis) of OT1 cells showed an increased rate of death on day 5 than on day 3-post antigen stimulation. The addition of only IL-12 or IGF-1 alone, but not of IL-2, IL-15 or T- α1, decreased OT1 cell apoptosis on day 3. These anti-apoptotic effects of IL-12 and IGF- 1, however, were recovered on day 5-post stimulation.
  
  
  CONCLUSIONS
  In conclusion, these results indicate that the activation phenotype and the survival of antigen-specific T cells can be differently modulated by immunomodulatory factors, where, interleukin-12 and IGF-1 induced the favorable effect. These results have a significant implication for T cell adoptive immunotherapy in different settings.
authors.affiliation: College of Applied Medical Sciences, Prince Salman University, Saudi Arabia. faris_alenzi@hotmail.com
authors.forename: F Q
authors.initials: FQ
authors.lastname: Alenzi
authors.forename: F A
authors.initials: FA
authors.lastname: Alenazi
authors.forename: Y
authors.initials: Y
authors.lastname: Al-Kaabi
authors.forename: M L
authors.initials: ML
authors.lastname: Salem
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D005434:Flow Cytometry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D019409:Interleukin-15; D007376:Interleukin-2; D018664:Interleukin-12; D014212:Tretinoin; D013947:Thymosin; D007334:Insulin-Like Growth Factor I; D000077596:Thymalfasin