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 an alysis to measure frequencies of alloreactive cytotoxic T cell precurs ors (CTLp) and interleukin (IL)-2-producing T helper cells (IL-2/HTLp) to assess the risk of graft-versus-host disease in bone marrow transp lantation (BMT). However, no test has been available to measure precur sor frequencies of the important IL-4-secreting subset. Methods. We ha ve now established a limiting dilution analysis to measure the frequen cy of IL-4-producing T helper cells (IL-4/HTLp) using the IL-4-respons ive 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 ass ess the relationship between the number of donor anti-recipient IL-4-s ecreting T cells and disease outcome. Results. Frequencies of IL-4/HTL p have been studied in HLA-identical siblings, HLA-''matched'' unrelat ed, and HLA-mismatched combinations and found to range from similar to 1/500,000 in HLA-identical sibling pairs to similar 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. Clini cal follow-up of 30 patients showed that high IL-4/HTLp frequencies ar e associated with a reduced risk of severe graft-versus-host disease. High IL-4/HTLp frequencies may also indicate an increased risk of leuk emia relapse. Conclusions. Our data suggest that measurement of IL-4/H TLp frequencies provides information distinct from that obtained with CTLp and IL-2/HTLp. This new assay provides a valuable additional meth od for optimizing donor selection in unrelated BMT.