Role of CD27 in T cell immune response. Analysis by recombinant soluble CD27.
CD27 is a disulfide-linked 120-kDa transmembrane glycoprotein expressed on the majority of T cells, B cells, and NK cells; it has homology to a family of molecules that includes the receptors for nerve growth factor and TNF. Previous studies strongly suggest that the CD27 molecule plays a key role in the process of T cell activation. To further determine its role in T cell activation, a recombinant soluble molecule composing only the extracellular domain of CD27 was produced by transfection of Chinese hamster ovary cells. We have defined the binding properties of recombinant soluble CD27 (rsCD27) to CD27 ligand (CD27L) cDNA transfected NIH 3T3 cells and have determined its functional effects on in vitro T cell activation as well as on PWM-driven B cell IgG synthesis. rsCD27 bound specifically to CD27L and the binding was inhibited by one of our anti-CD27 mAbs, anti-1A4, suggesting that the 1A4 epitope of CD27 plays a role in the binding to CD27L. Functionally, rsCD27 inhibited T cell proliferation induced by various stimuli, such as PHA, tetanus toxoid, and anti-CD2, as well as PWM-driven B cell IgG synthesis, similar to the effects of adding anti-1A4. Determination of CD27L expression showed that CD27L mRNA is induced rapidly on activated T and B cells. Taken together, these results provide direct evidence that CD27-CD27L interaction plays a critical role in T cell activation as well as in T cell-dependent B cell IgG synthesis, suggesting that the CD27-CD27L interaction may constitute a component of the T cell-T cell or T cell-B cell interaction seen after activation with Ag or mitogen.
Agematsu
K
K
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Kobata
T
T
Sugita
K
K
Freeman
G J
GJ
Beckmann
M P
MP
Schlossman
S F
SF
Morimoto
C
C
D000917:Antibody Formation; D015703:Antigens, CD; D001483:Base Sequence; D053282:CD27 Ligand; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D008024:Ligands; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000502:physiology*
D015703:Antigens, CD; D053282:CD27 Ligand; D017931:DNA Primers; D008024:Ligands; D008565:Membrane Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7