Interleukin 2 receptor (Tac antigen) expression in HTLV-I-associated adult T-cell leukemia.
Interleukin-2 (IL-2) is a lymphokine synthesized by some T-cells following activation. Resting T-cells do not express IL-2 receptors, but receptors are rapidly expressed on T-cells following interaction of antigens, mitogens, or monoclonal antibodies with the antigen-specific T-cell receptor complex. Using anti-Tac, a monoclonal antibody that recognizes the IL-2 receptor, the receptor has been purified and shown to be a Mr 33,000 peptide that is posttranslationally glycosylated to a Mr 55,000 mature form. Normal resting T-cells and most leukemic T-cell populations do not express IL-2 receptors; however, the leukemic cells of the 11 patients examined who had human T-cell lymphotropic virus-associated adult T-cell leukemia expressed the Tac antigen. In human T-cell lymphotropic virus-I infected cells, the Mr 42,000 long open reading frame protein encoded in part by the pX region of this virus may act as a transacting transcriptional activator that induces IL-2 receptor gene transcription, thus providing an explanation for the constant association of IL-2 receptor expression with adult T-cell lymphotropic virus-I infection of lymphoid cells. The constant expression of large numbers of IL-2 receptors which may be aberrant may play a role in the uncontrolled growth of adult T-cell leukemia cells. Two patients with Tac-positive adult T-cell leukemia have been treated with the anti-Tac. One of the patients had 6- and 3-mo remissions of his leukemia following two courses of therapy with this monoclonal antibody directed toward this growth factor receptor.
Waldmann
T A
TA
Longo
D L
DL
Leonard
W J
WJ
Depper
J M
JM
Thompson
C B
CB
Krönke
M
M
Goldman
C K
CK
Sharrow
S
S
Bongiovanni
K
K
Greene
W C
WC
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002460:Cell Line; D017977:Deltaretrovirus / Q000235:genetics; D005814:Genes, Viral; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000382:microbiology* / Q000628:therapy; D008213:Lymphocyte Activation; D008297:Male; D011971:Receptors, Immunologic / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology / Q000302:isolation & purification; D015375:Receptors, Interleukin-2; D012192:Retroviridae Infections / Q000097:blood / Q000382:microbiology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000382:microbiology; D014157:Transcription Factors; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology
D000911:Antibodies, Monoclonal; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D014157:Transcription Factors; D014764:Viral Proteins