Functional effects of CD30 on a large granular lymphoma cell line, YT. Inhibition of cytotoxicity, regulation of CD28 and IL-2R, and induction of homotypic aggregation.
Studies are described revealing novel regulatory functions for the lymphocyte activation Ag CD30. A new mAb, C10, reactive with YT cells binds to CD30 and induces inhibition of the cytotoxicity of YT for Raji cells. C10 inhibition of cytotoxicity requires several hours preincubation of YT with C10; the antibody has no effect if added directly to YT cytotoxicity assays. CD30 stimulation by C10 down-regulates CD28 expression on YT by > 80% within 48 h. Because CD28 is required for YT cytotoxicity toward Raji cells and other B7/BB1 bearing targets, it is suggested that inhibition of cytotoxicity of YT is mediated by control of CD28 expression and/or signaling via CD30. Accordingly, conjugation of YT with Raji is only slightly affected by CD30-mediated down-regulation of CD28, and perforin mRNA steady state levels are not changed at all. C10 treatment of YT cells additionally down-regulates the expression CD45 and up-regulates IL-2R p55. Moreover, CD30 stimulation by C10 causes homotypic aggregation of YT. Homotypic aggregation is slow, requiring gene transcription, translation, metabolic energy at elevated temperature (37 degrees C), magnesium ions, and an intact cytoskeleton. These studies offer insights into the function of CD30 as a complex regulator of T cells.
Bowen
M A
MA
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.
Olsen
K J
KJ
Cheng
L
L
Avila
D
D
Podack
E R
ER
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018106:CD28 Antigens / Q000032:analysis* / Q000235:genetics; D002449:Cell Aggregation; D003602:Cytotoxicity, Immunologic; D017730:Ki-1 Antigen / Q000502:physiology*; D008223:Lymphoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017730:Ki-1 Antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D054353:Perforin