title: CCR7+ central and CCR7- effector memory CD4+ T cells in human cutaneous leishmaniasis.
abstract: OBJECTIVE
  The profile of central (=T(CM)) and effector (=T(EM)) memory CD4(+) T cell subsets and the possible role as surrogate markers of protection is studied in the volunteers with history of cutaneous leishmaniasis (HCL).
  
  
  METHODS
  Profile of T cell subsets based on CCR7/CD45RA expressions and phenotypic changes after soluble Leishmania antigen (SLA) stimulation were analyzed. Then, sorted CD4(+)CD45RO(-)CD45RA(+) naïve T, CD4(+)CD45RO(+)CD45RA(-)CCR7(-) T(EM,) CD4(+)CD45RO(+)CD45RA(-)CCR7(+) T(CM) subsets were cultured with SLA for proliferation, cytokine production and intracellular cytokine assays.
  
  
  RESULTS
  In the HCL and control volunteers, the mean frequencies of CD4(+)CD45RA(+)CCR7(+) naïve T cells and CD4(+)CD45RA(-)CCR7(-) T(EM) cells were higher than the other subsets before culture. Frequency of naïve T cells and CD4(+)CD45RA(-)CCR7(+) T(CM) cells was significantly decreased (P=0.01 for naïve T and P<0.05 for T(CM) cells) and frequency of T(EM) cells was significantly increased after SLA stimulation compared to before culture (P<0.001). By CFSE labeling, CD4(+)CD45RO(+)CD45RA(-)CCR7(+) T(CM) cells showed more proliferation potential than CD4(+)CD45RO(+)CD45RA(-)CCR7(-) T(EM) cells. Stimulation of the T(EM) cells in HCL volunteers induced a significantly higher IFN-γ production (P=0.04) with higher number of intracellular IFN-γ positive cells (P=0.032) than the same cells from controls. A significantly higher number of T(CM) cells produced IL-2 in HCL volunteers compared with controls (P<0.05). Most of the intracellular IFN-γ positive T(EM) cells were proliferating CFSE-dim populations (P<0.05).
  
  
  CONCLUSIONS
  A combination of Leishmania-reactive IFN-γ producing CD4(+)CD45RO(+)CD45RA(-)CCR7(-) T(EM) and Leishmania-reactive IL-2 producing CD4(+)CD45RO(+)CD45RA(-)CCR7(+) T(CM) are identified in individuals with history of CL which might play a role in protective recall immune response against Leishmania infection.
authors.affiliation: Medical Parasitology and Mycology Department, School of Public Health, Tehran University of Medical Sciences, P.O. Box 14155-6446, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Keshavarz Valian
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Nateghi Rostami
authors.forename: Minoo
authors.initials: M
authors.lastname: Tasbihi
authors.forename: Akram
authors.initials: A
authors.lastname: Miramin Mohammadi
authors.forename: Seyed Ebrahim
authors.initials: SE
authors.lastname: Eskandari
authors.forename: Abdolfattah
authors.initials: A
authors.lastname: Sarrafnejad
authors.forename: Ali
authors.initials: A
authors.lastname: Khamesipour
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000469:parasitology; D002478:Cells, Cultured; D018920:Coculture Techniques; D060467:Disease Resistance / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D054400:Receptors, CCR7 / Q000096:biosynthesis* / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology* / Q000469:parasitology
chemical_list: D015415:Biomarkers; C515370:CCR7 protein, human; D054400:Receptors, CCR7