title: Phenotypic characterization of Plasmodium berghei responsive CD8+ T cells after immunization with live sporozoites under chloroquine cover.
abstract: BACKGROUND
  An effective malaria vaccine remains elusive. The most effective experimental vaccines confer only limited and short-lived protection despite production of protective antibodies. However, immunization with irradiated sporozoites, or with live sporozoites under chloroquine cover, has resulted in long-term protection apparently due to the generation of protective CD8+ T cells. The nature and function of these protective CD8+ T cells has not been elucidated. In the current study, the phenotype of CD8+ T cells generated after immunization of C57BL/6 mice with live Plasmodium berghei sporozoites under chloroquine cover was investigated.
  
  
  METHODS
  Female C57BL/6 mice, C57BL/6 mice B2 macroglobulin -/- [KO], or invariant chain-/- [Ic KO] [6-8 weeks old] were immunized with P. berghei sporozoites and treated daily with 800 μg/mouse of chloroquine for nine days. This procedure of immunization is referred to as "infection/cure". Mice were challenged by inoculating intravenously 1,000 infectious sporozoites. Appearance of parasitaemia was monitored by Giemsa-stained blood smears.
  
  
  RESULTS
  By use of MHC I and MHC II deficient animals, results indicate that CD8+ T cells are necessary for full protection and that production of protective antibodies is either CD4+ T helper cells dependent and/or lymphokines produced by CD4 cells contribute to the protection directly or by helping CD8+ T cells. Further, the phenotype of infection/cure P. berghei responsive CD8+ T cells was determined to be KLRG1high CD27low CD44high and CD62Llow.
  
  
  CONCLUSIONS
  The KLRG1high CD27low CD44high and CD62Llow phenotype of CD8+ T cells is associated with protection and should be investigated further as a candidate correlate of protection.
authors.forename: Clara
authors.initials: C
authors.lastname: Brando
authors.forename: Jason H
authors.initials: JH
authors.lastname: Richardson
authors.forename: Jittawadee
authors.initials: J
authors.lastname: Murphy
authors.forename: Christian F
authors.initials: CF
authors.lastname: Ockenhouse
authors.affiliation: Military Malaria Research Program, Malaria Vaccine Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910, USA. edwin.kamau@us.army.mil.
authors.forename: Edwin
authors.initials: E
authors.lastname: Kamau
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D002738:Chloroquine / Q000008:administration & dosage*; D005260:Female; D007114:Immunization / Q000379:methods*; D016130:Immunophenotyping; D037181:Lectins, C-Type; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000276:immunology*; D011971:Receptors, Immunologic / Q000032:analysis; D034101:Sporozoites / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D017780:Malaria Vaccines; D011971:Receptors, Immunologic; D002738:Chloroquine