Molecular interaction between CD58 and CD2 counter-receptors mediates the ability of monocytes to augment T cell activation by IL-12.
IL-12 stimulates both T and NK cells and is pivotal in the development of the Th1 immune response. In this work, we show that an interaction between CD2 and CD58 on activated T cells and monocytes, respectively, regulates the T cell response to IL-12. B cells provide little IL-12-specific costimulation, and this correlates with the low level of CD58 on B cells relative to monocytes and the lack of significant up-regulation in response to IFN-gamma or PHA activation. CHO cell transfectants expressing CD58 at a level comparable with that found on monocytes restore IL-12 responsiveness to APC-depleted T cells. This effect is not observed with CHO cells expressing CD48, a second CD2 ligand with a low avidity for CD2 relative to CD58. Thus, in addition to augmenting adhesion between T cells and their cognate APCs and facilitating TCR-triggered activation, the CD2-CD58 interaction uniquely optimizes the T cell response to IL-12.
Gollob
J A
JA
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Li
J
J
Kawasaki
H
H
Daley
J F
JF
Groves
C
C
Reinherz
E L
EL
Ritz
J
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001667:Binding, Competitive / Q000276:immunology; D018801:CD2 Antigens / Q000494:pharmacology*; D018968:CD58 Antigens / Q000096:biosynthesis / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000378:metabolism; D053707:Receptors, Interleukin-12; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D018968:CD58 Antigens; D010835:Phytohemagglutinins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12