title: Association between interleukin-4-producing T lymphocyte frequencies and reduced risk of graft-versus-host disease.
abstract: BACKGROUND
  We have previously developed and used limiting dilution analysis to measure frequencies of alloreactive cytotoxic T cell precursors (CTLp) and interleukin (IL)-2-producing T helper cells (IL-2/HTLp) to assess the risk of graft-versus-host disease in bone marrow transplantation (BMT). However, no test has been available to measure precursor frequencies of the important IL-4-secreting subset.
  
  
  METHODS
  We have now established a limiting dilution analysis to measure the frequency of IL-4-producing T helper cells (IL-4/HTLp) using the IL-4-responsive indicator cell line CT.h4S and have applied this assay to measure alloreactive IL-4/HTLp frequencies in BMT donor-recipient pairs. These frequencies were then analyzed in the context of clinical data to assess the relationship between the number of donor anti-recipient IL-4-secreting T cells and disease outcome.
  
  
  RESULTS
  Frequencies of IL-4/HTLp have been studied in HLA-identical siblings, HLA-"matched" unrelated, and HLA-mismatched combinations and found to range from approximately 1/500,000 in HLA-identical sibling pairs to -1/2,000 in HLA-DR-mismatched pairs. These frequencies were independent of those for IL-2/HTLp and showed a negative correlation with those for CTLp. Clinical follow-up of 30 patients showed that high IL-4/HTLp frequencies are associated with a reduced risk of severe graft-versus-host disease. High IL-4/HTLp frequencies may also indicate an increased risk of leukemia relapse.
  
  
  CONCLUSIONS
  Our data suggest that measurement of IL-4/HTLp frequencies provides information distinct from that obtained with CTLp and IL-2/HTLp. This new assay provides a valuable additional method for optimizing donor selection in unrelated BMT.
authors.affiliation: Department of Immunology and Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, England.
authors.forename: N
authors.initials: N
authors.lastname: Imami
authors.forename: P A
authors.initials: PA
authors.lastname: Brookes
authors.forename: G
authors.initials: G
authors.lastname: Lombardi
authors.forename: B
authors.initials: B
authors.lastname: Hakooz
authors.forename: M
authors.initials: M
authors.lastname: Johns
authors.forename: J M
authors.initials: JM
authors.lastname: Goldman
authors.forename: J R
authors.initials: JR
authors.lastname: Batchelor
authors.forename: R I
authors.initials: RI
authors.lastname: Lechler
authors.forename: M A
authors.initials: MA
authors.lastname: Ritter
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000502:physiology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D012307:Risk Factors; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D006680:HLA Antigens; D007376:Interleukin-2; D015847:Interleukin-4