title: Expression of the memory marker CD45RO on helper T cells in macaques.
abstract: BACKGROUND
  In humans it has been reported that a major site of the latent reservoir of HIV is within CD4+ T cells expressing the memory marker CD45RO, defined by the mAb UCHL1. There are conflicting reports regarding the expression of this antigen in macaques, the most relevant animal species for studying HIV pathogenesis and testing new therapies. There is now a major effort to eradicate HIV reservoirs and cure the infection. One approach is to eliminate subsets of cells housing the latent reservoir, using UCHL1 to target these cells. So that such studies may be performed in macaques, it is essential to determine expression of CD45RO.
  
  
  METHODS
  We have used immunofluorescence and flow cytometry to study cell surface expression of CD45RO on lymphocytes from PBMC, lymphoid, and GI organs of rhesus, pigtailed, and cynomolgus macaques. Both direct and indirect immunofluorescence experiments were performed.
  
  
  RESULTS
  CD45RO is expressed on a subset of CD4+ lymphocytes of all pigtailed, a fraction of rhesus, and neither of the cynomolgus macaques studied. The binding of UCHL1 to macaque cells was of lower avidity than to human cells. This could be overcome by forming UCHL1 multimers. Directly conjugating fluors to UCHL1 can inhibit UCHL1 binding to macaque cells. Patterns of UCHL1 expression differ somewhat in macaques and humans, and from that of other memory markers often used in macaques.
  
  
  CONCLUSIONS
  CD45RO, defined with mAb UCHL1, is well expressed on CD4+ cells in pigtailed macaques. Using tissues recovered from latently infected pigtailed macaques we are determining whether UCHL1, or other memory markers, can define the cellular locus of the reservoir. The low avidity of this interaction could limit the utility of UCHL1, in its conventional form, to eliminate cells in vivo and test this approach in macaque models of HIV infection.
authors.affiliation: Research Institute for Children, Children's Hospital, New Orleans, Louisiana, United States of America ; Departments of Microbiology, Immunology and Parasitology, LSU Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Valentine
authors.forename: Kejing
authors.initials: K
authors.lastname: Song
authors.forename: Grace A
authors.initials: GA
authors.lastname: Maresh
authors.forename: Heather
authors.initials: H
authors.lastname: Mack
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Huaman
authors.forename: Patricia
authors.initials: P
authors.lastname: Polacino
authors.forename: On
authors.initials: O
authors.lastname: Ho
authors.forename: Anthony
authors.initials: A
authors.lastname: Cristillo
authors.forename: Hye
authors.initials: H
authors.lastname: Kyung Chung
authors.forename: Shiu-Lok
authors.initials: SL
authors.lastname: Hu
authors.forename: Seth H
authors.initials: SH
authors.lastname: Pincus
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D000922:Immunotoxins / Q000633:toxicity; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008251:Macaca; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D000922:Immunotoxins; D017493:Leukocyte Common Antigens
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