CD2-CD48 interactions promote cytotoxic T lymphocyte induction and function: anti-CD2 and anti-CD48 antibodies impair cytokine synthesis, proliferation, target recognition/adhesion, and cytotoxicity.
The role of CD2 signaling in cytotoxic T lymphocyte (CTL) development was examined by stimulating mouse T cells with anti-CD3 monoclonal antibody (mAb) in the absence or presence of anti-CD2 mAb or anti-CD48 mAb or both. Induction of nonspecific CTL and interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) synthesis were impaired in the absence of CD2-CD48 interactions. Anti-CD2 mAb also inhibited activation-induced expression of the high-affinity IL-2 receptor (IL-2R). In contrast, IFN-gamma receptor (IFNGR) expression was increased in the presence of anti-CD2 mAb. Reduced cytotoxicity by CTL induced in the absence of CD2-CD48 interactions was associated with a diminished ability of CTL to conjugate with target cells and reduced expression of granzyme B and perforin. Anti-CD2 mAb did not affect expression of Fas ligand and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by anti-CD3-activated T cells. Cytotoxic effector function and granzyme B and perforin expression were rescued when exogenous IL-2 and IFN-gamma were added in combination with anti-CD2 mAb to anti-CD3-activated T cells at initiation of culture. We conclude that CD2-CD48 interactions during T cell activation are critical for the synthesis of sufficient IL-2 and IFN-gamma to drive CD8(+) T cells to differentiate into functional cytotoxic effector cells.
Department of Microbiology & Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada.
Bruce L
BL
Musgrave
Carrie L
CL
Watson
David W
DW
Hoskin
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D018801:CD2 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D000071178:CD48 Antigen; D002448:Cell Adhesion; D002455:Cell Division; D016207:Cytokines / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D053804:Granzymes; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000187:drug effects; D012697:Serine Endopeptidases / Q000187:drug effects / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018801:CD2 Antigens; D017252:CD3 Complex; D000071178:CD48 Antigen; C000604066:Cd48 protein, mouse; D016207:Cytokines; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D015375:Receptors, Interleukin-2; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases