Association between interleukin-4-producing T lymphocyte frequencies and reduced risk of graft-versus-host disease.
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.
Imami
N
N
Department of Immunology and Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, England.
Brookes
P A
PA
Lombardi
G
G
Hakooz
B
B
Johns
M
M
Goldman
J M
JM
Batchelor
J R
JR
Lechler
R I
RI
Ritter
M A
MA
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*
D006680:HLA Antigens; D007376:Interleukin-2; D015847:Interleukin-4