Histidine-rich glycoprotein blocks T cell rosette formation and modulates both T cell activation and immunoregulation.
Histidine-rich glycoprotein (HRGP) is a plasma and platelet protein with undefined function in vivo. It has been reported to inhibit rosette formation between murine T cells and erythrocytes. We have shown that HRGP binds specifically to human T lymphocytes but not sheep erythrocytes and have demonstrated a 56-kDa HRGP-binding protein on the T cell surface which is distinct from the CD2 sheep erythrocyte receptor. We have now investigated whether HRGP can inhibit human T cell-sheep erythrocyte rosette formation and whether HRGP can modulate T cell activation. HRGP at physiologic concentrations specifically inhibited rosette formation between human T lymphocytes and sheep erythrocytes. HRGP suppressed proliferation of antigen receptor (CD3)-triggered T cells induced by interleukin 2; this suppression was specifically reversed by prior incubation of HRGP with affinity-purified anti-HRGP IgG. Addition of HRGP 12-24 h after CD3 triggering no longer suppressed T cell proliferation, suggesting HRGP suppressed T cell division by interfering with one or more early events in the process of T cell activation. Human serum (containing 100-150 micrograms/ml HRGP) was also capable of suppressing T cell proliferation; serum which had been immunodepleted of HRGP no longer inhibited T cell proliferation. Furthermore, HRGP inhibited interleukin 2 receptor expression on activated T cells, causing decreased T cell interferon-gamma release and altered T cell-dependent inhibition of erythropoiesis. HRGP is thus capable of modulating T cell activation and T cell immunoregulation; HRGP may function as a natural suppressive regulator of human T lymphocyte activation.
Shatsky
M
M
Department of Medicine, Stanford University Medical Center, California 94305.
Saigo
K
K
Burdach
S
S
Leung
L L
LL
Levitt
L J
LJ
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002455:Cell Division / Q000187:drug effects; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects; D006023:Glycoproteins; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism; D012397:Rosette Formation; D012756:Sheep; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D000099053:Histidine-Rich Glycoprotein
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D006023:Glycoproteins; D007376:Interleukin-2; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D000099053:Histidine-Rich Glycoprotein; D007371:Interferon-gamma