The complement receptor 1, CR1 (CD35), mediates inhibitory signals in human T-lymphocytes.
The modulation the specific, adaptive immune response by complement, particularly of by complement C3, is mainly attributed to its interaction with complement receptors on B-lymphocytes. The function of complement receptors on T-lymphocytes, in contrast, is less well understood, although expression of the complement receptor (CR)1 and CR3 on T-cells has been described years ago. In the present study we investigated the effect of antibodies to CR1 on T-cell lines and peripheral T-cells of healthy donors, respectively. Antibodies to CR1 profoundly inhibited the proliferation of the T-cells; of note is, that exogenously added interleukin 2, though enhancing proliferation, did not overcome the inhibitory effect mediated by anti-CR1. While anti-CR1 had no effect on the activation of the immediate early genes c-jun or c-fos nor on the early increase of gamma interferon- or interleukin 2-specific RNA, the protein synthesis of those cytokines was inhibited. Moreover, synthesis of the proliferating cell nuclear antigen (PCNA) was reduced as was the expression of cyclins, particularly of cyclin A and cyclin D3. Taken together, the data indicate that triggering CR1 inhibits proliferation of T-lymphocytes by a mechanism operating downstream of the initial signalling events.
Wagner
Christof
C
Institut für Immunologie der Universität Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.
Ochmann
Carsten
C
Schoels
Margarita
M
Giese
Thomas
T
Stegmaier
Sabine
S
Richter
Rosi
R
Hug
Friederike
F
Hänsch
G Maria
GM
D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D016213:Cyclins / Q000096:biosynthesis; D017781:Genes, Immediate-Early; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D017463:Receptors, Complement 3b / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*
D016213:Cyclins; D007376:Interleukin-2; D018809:Proliferating Cell Nuclear Antigen; D017463:Receptors, Complement 3b; D007371:Interferon-gamma