T-lymphocyte response to cytokines in B-chronic lymphocytic leukemia.
The mechanisms underlying abnormal T-cell function in B-chronic lymphocytic leukemia (B-CLL) are unknown. We have studied B-CLL T-cell activation pathways in the rigorous absence of leukemic cells and with controlled numbers of accessory cells present. The responsiveness to added recombinant IL-1 and IL-2 was assessed. We have found that under optimal culture conditions B-CLL T cells had a normal PHA-induced proliferative response in terms of incorporated 3H-thymidine per T cell. Also the capacity of mitomycin-C treated B-CLL monocytes to support autologous T-cell mitogenesis was normal. However, a subtle difference between normal and B-CLL T cells emerged with respect to cytokine responsiveness. While the PHA response of purified normal T cells in the absence of monocytes was augmented by rIL-1, this could not be demonstrated for B-CLL T cells. A much greater degree of augmentation occurred with added rIL-2 in the case of both normal and B-CLL T cells. In the presence of 20% autologous monocytes rIL-1 and rIL-2 had no effect on mitogenesis. We conclude that B-CLL T cells have an abnormal profile of cytokine responsiveness which is consistent with observed abnormalities of subset distribution, and which may contribute to the clinical immunodeficiency in B-CLL.
Department of Nephrology, Prince Henry's Hospital, Melbourne, Australia.
P G
PG
Briggs
N
N
Kraft
R C
RC
Atkins
D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D016685:Mitomycin / Q000494:pharmacology; D009000:Monocytes / Q000502:physiology; D010835:Phytohemagglutinins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D016685:Mitomycin