title: Blood feeding by the Rocky Mountain spotted fever vector, Dermacentor andersoni, induces interleukin-4 expression by cognate antigen responding CD4+ T cells.
abstract: BACKGROUND
  Tick modulation of host defenses facilitates both blood feeding and pathogen transmission. Several tick species deviate host T cell responses toward a Th2 cytokine profile. The majority of studies of modulation of T cell cytokine expression by ticks were performed with lymphocytes from infested mice stimulated in vitro with polyclonal T cell activators. Those reports did not examine tick modulation of antigen specific responses. We report use of a transgenic T cell receptor (TCR) adoptive transfer model reactive with influenza hemagglutinin peptide (110-120) to examine CD4+ T cell intracellular cytokine responses during infestation with the metastriate tick, Dermacentor andersoni, or exposure to salivary gland extracts.
  
  
  RESULTS
  Infestation with pathogen-free D. andersoni nymphs or administration of an intradermal injection of female or male tick salivary gland extract induced significant increases of IL-4 transcripts in skin and draining lymph nodes of BALB/c mice as measured by quantitative real-time RT-PCR. Furthermore, IL-10 transcripts were significantly increased in skin while IL-2 and IFN-gamma transcripts were not significantly changed by tick feeding or intradermal injection of salivary gland proteins, suggesting a superimposed Th2 response. Infestation induced TCR transgenic CD4+ T cells to divide more frequently as measured by CFSE dilution, but more notably these CD4+ T cells also gained the capacity to express IL-4. Intracellular levels of IL-4 were significantly increased. A second infestation administered 14 days after a primary exposure to ticks resulted in partially reduced CFSE dilution with no change in IL-4 expression when compared to one exposure to ticks. Intradermal inoculation of salivary gland extracts from both male and female ticks also induced IL-4 expression.
  
  
  CONCLUSIONS
  This is the first report of the influence of a metastriate tick on the cytokine profile of antigen specific CD4+ T cells. Blood feeding by D. andersoni pathogen-free nymphs or intradermal injection of salivary gland extracts programs influenza hemagglutinin influenza peptide specific TCR transgenic CD4+ T cells to express IL-4.
authors.affiliation: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases and Center for Tropical Diseases, School of Medicine, University of Texas Medical Branch, Galveston, Texas, 77555, USA. skwikel@utmb.edu.
authors.forename: Venkata D
authors.initials: VD
authors.lastname: Boppana
authors.forename: Saravanan
authors.initials: S
authors.lastname: Thangamani
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Alarcon-Chaidez
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Adler
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Wikel