CD2-CD48 interactions promote interleukin-2 and interferon-gamma synthesis by stabilizing cytokine mRNA.
CD2-CD48 interactions enhance T cell receptor-driven mouse T lymphocyte activation. However, the mechanism is not well understood. Here we show that blockade of CD2-CD48 interactions with anti-CD48 monoclonal antibody (mAb) inhibited interleukin (IL)-2 and interferon (IFN)-gamma expression, as well as T cell proliferation in response to mitogenic anti-CD3 mAb, although more potent inhibition resulted from blocking CD28-CD80/CD86 interactions. Blockade of both CD2 and CD28 costimulation abrogated T cell proliferation and cytokine synthesis. Conversely, T cells stimulated with immobilized anti-CD3 and anti-CD2 mAb exhibited increased proliferation and IL-2 and IFN-gamma expression, although a stronger enhancing effect was obtained with immobilized anti-CD3 and anti-CD28 mAb. Concurrent CD2 and CD28 costimulation caused a further increase in proliferation and cytokine synthesis. Stimulation of purified T cells with microsphere-immobilized anti-CD3 and anti-CD2 mAb increased IL-2 and IFN-gamma mRNA stability. However, CD28 costimulation had a stronger enhancing effect on IL-2 and IFN-gamma mRNA stability that was not further increased by concomitant CD2 signaling. CD2, therefore, costimulates T cell activation by stabilizing cytokine mRNA transcripts, albeit with less efficiency than CD28.
Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 1X5, Canada.
Bruce L
BL
Musgrave
Carrie L
CL
Watson
S M Mansour
SM
Haeryfar
Christine A
CA
Barnes
David W
DW
Hoskin
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D018801:CD2 Antigens / Q000378:metabolism*; D017252:CD3 Complex / Q000276:immunology; D000071178:CD48 Antigen; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D051379:Mice; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018801:CD2 Antigens; D017252:CD3 Complex; D000071178:CD48 Antigen; C000604066:Cd48 protein, mouse; D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; D007371:Interferon-gamma