title: Long-term effects of alemtuzumab on regulatory and memory T-cell subsets in kidney transplantation.
abstract: BACKGROUND
  Induction with lymphocyte-depleting antibodies is routinely used to prevent rejection but often skews T cells toward memory. It is not fully understood which memory and regulatory T-cell subsets are most affected and how they relate to clinical outcomes.
  
  
  METHODS
  We analyzed T cells from 57 living-donor renal transplant recipients (12 reactive and 45 quiescent) 2.8±1.4 years after alemtuzumab induction. Thirty-four healthy subjects and nine patients with acute cellular rejection (ACR) were also studied.
  
  
  RESULTS
  We found that alemtuzumab caused protracted CD4 more than CD8 T-lymphocyte deficiency, increased proportion of CD4 memory T cells, and decreased proportion of CD4 regulatory T cells. Reactive patients exhibited higher proportions of CD4 effector memory T cells (TEM) and CD8 terminally differentiated TEM (TEMRA), with greater CD4 TEM and CD8 TEMRA to regulatory T cell ratios, than quiescent patients or healthy controls. Patients with ongoing ACR had profound reduction in circulating CD8 TEMRA. Mixed lymphocyte assays showed significantly lower T-cell proliferation to donor than third-party antigens in the quiescent group, while reactive and ACR patients exhibited increased effector molecules in CD8 T cells.
  
  
  CONCLUSIONS
  Our findings provide evidence that T-cell skewing toward TEM may be associated with antigraft reactivity long after lymphodepletion. Further testing of TEM and TEMRA subsets as rejection predictors is warranted.
authors.affiliation: Human Immunology Program, Thomas E. Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Camila
authors.initials: C
authors.lastname: Macedo
authors.forename: John T
authors.initials: JT
authors.lastname: Walters
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Orkis
authors.forename: Kumiko
authors.initials: K
authors.lastname: Isse
authors.forename: Beth D
authors.initials: BD
authors.lastname: Elinoff
authors.forename: Sheila P
authors.initials: SP
authors.lastname: Fedorek
authors.forename: John M
authors.initials: JM
authors.lastname: McMichael
authors.forename: Geetha
authors.initials: G
authors.lastname: Chalasani
authors.forename: Parmjeet
authors.initials: P
authors.lastname: Randhawa
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Demetris
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
authors.forename: Henkie
authors.initials: H
authors.lastname: Tan
authors.forename: Ron
authors.initials: R
authors.lastname: Shapiro
authors.forename: Doug
authors.initials: D
authors.lastname: Landsittel
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Lakkis
authors.forename: Diana
authors.initials: D
authors.lastname: Metes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D016559:Tacrolimus / Q000627:therapeutic use; D013995:Time; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D009173:Mycophenolic Acid; D016559:Tacrolimus; D008775:Methylprednisolone