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

Abstract

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.

Roles of CD48 in regulating immunity and tolerance

“…Both anti-CD2 and anti-CD48 mAbs reduced IL-2Rα expression, IL-2 and IFNγ production, and target lysis by anti-CD3-stimulated bulk T cells in vitro . The reduced target lysis could be rescued by addition of IL-2 [95], suggesting that CD48:CD2 costimulation may stabilize IL-2 mRNA [96]. Thus, CD48:CD2 interactions contribute to both priming and effector functions of CD8+ T cells.…”

The CD2 Family of Natural Killer Cell Receptors

“…For instance, CD2 promotes T cell conjugation with antigen-presenting cells , and T cell cytokine mRNA stability is increased by CD2-CD48 interaction (Musgrave et al 2003(Musgrave et al , 2004. Likewise, CD2 is important in NK-target adhesion (Timonen et al 1990;Voltarelli et al 1993;Barber and Long 2003), and because NK cells are activated by antigen-presenting cells (Degli-Esposti and Smyth 2005), CD2 engagement may also enhance these interactions.…”

Exchange of Cytosolic Content between T Cells and Tumor Cells Activates CD4 T Cells and Impedes Cancer Growth

“…We tested the involvement of classical molecules expressed on T cells enabling cell-cell contacts of T cells with targets as reported for selectins [31] and integrins [32] as well as the involvement of CD2 [33] but none of these molecules were inevitable for the exchange of cytosol (data not shown). The data suggest an expression of a molecule of unspecific nature since in the mouse model, the molecule expression seems to be common for both T and B cells.…”