ANTI-CD48 (MURINE CD2 LIGAND) MABS SUPPRESS CELL-MEDIATED-IMMUNITY IN-VIVO

With the identification of murine CD48 as a homolog of the human CD2 l igand LFA-3 (CD58) and as a ligand itself for murine CD2, the anti-mur ine CD48 mAb HM48-1 was administered intravenously to investigate the role of CD48 in cell mediated immunity in vivo. Anti-CD48 mAb diminish ed the contact sensitivity response to the hapten trinitrophenol (TNP) . mAb also inhibited in vivo priming for the subsequent generation of secondary, TNP-specific, cytotoxic T lymphocytes (CTL) in vitro. The i nhibitory effect was most effective in the afferent or inductive phase of immunity for CTL, while anti-CD48 mAb was most inhibitory for the efferent or elicitative phase of contact sensitivity. Addition of anti -CD48 mAb directly to secondary CTL cultures also completely inhibited CTL generation, while addition to the lytic assay showed only minimal inhibition of CTL activity. Combining cells from mAb treated and untr eated animals showed no evidence for suppressor cells. Further experim ents revealed that mAb administered in vivo, as well as to culture, in hibited development of primary, alloantigen-specific CTL in vitro. Mix ed lymphocyte reaction and phytohemagglutinin proliferation were parti ally suppressed by mAb administered in vivo or in vitro, whereas other mitogenic responses remained unaffected. Flow cytometric analysis rev ealed a moderate down modulation of CD48, CD3 and CD8 after treatment with anti-CD48. However, this did not represent T cell depletion since CD2, Thy-1.2 and Ig expression did not change. These results support a major unrecognized role for CD48 in diverse aspects of cell mediated immunity, affecting both CD4+ and CD8+ effector T cell function. The anti-CD48 mAb functions not by depleting relevant T cell populations, but rather by altering the array of cell surface receptors, and subseq uent responses to primary and secondary antigenic challenge.