Recombinant human interleukin-2 restores in vitro T-cell colony formation by peripheral blood mononuclear cells after autologous bone marrow transplantation.
Immune reconstitution after autologous bone marrow transplantation (ABMT) was studied in peripheral blood by phytohemagglutinin stimulated T-cell colony formation (CFU-TL) and by surface phenotype analysis of T-lymphocytes with monoclonal antibodies. Twenty-six patients (15 small-cell lung cancer, 5 lymphoma, 3 acute myeloid leukemia [AML], 2 germ cell cancer, and 1 melanoma) were conditioned with high-dose multiple drug combinations (plus total body irradiation in AML patients). No maintenance chemotherapy was given following treatment. Despite a rapid return to normal values of peripheral T3+, T11+ lymphocytes, the T4/T8 ratio remained below 1.0 up to 24 months after transplant, regardless of infection by cytomegalovirus (CMV). A high percentage (26% +/- 3%) of lymphocyte cells with immature phenotype (T8+, Ia+) was found during the first 6 months after transplant. Out of 84 cultures, performed in 26 patients, no growth was observed in 47 instances (22 patients) up to 28 months after grafting. Growth occurred in 37 cultures (11 patients, from 1 to 51 months after transplant) although it never reached the colony numbers of normal controls. Recombinant human interleukin-2 (rIL-2) added to lymphocyte culture induced proliferation in 8 (4 CMV-positive and 4 CMV-negative patients) out of 12 instances of no growth. In cases of depressed CFU-TL (20 cultures), rIL-2 induced a 48% and 92% increase in six CMV-positive patients and nine CMV-negative patients, respectively. These observations show that after ABMT and regardless of CMV status, defects in CFU-TL can be partially corrected by rIL-2.
Bosly
A E
AE
Research Unit for Blood Diseases, Catholic University of Louvain, Brussels, Belgium.
Staquet
P J
PJ
Doyen
C M
CM
Chatelain
B J
BJ
Humblet
Y P
YP
Symann
M L
ML
D001773:Blood Cells / Q000166:cytology / Q000187:drug effects; D016026:Bone Marrow Transplantation; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D013601:T-Lymphocytes / Q000145:classification / Q000166:cytology* / Q000187:drug effects
D007376:Interleukin-2; D011994:Recombinant Proteins