Anti-CD48 (murine CD2 ligand) mAbs suppress cell mediated immunity in vivo

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Abstract
With the identification of murine CD48 as a homolog of the human CD2 ligand LFA-3 (CD58) and as a ligand itself for murine CD2, the antl-murine CD48 mAb HM48-1 was administered intravenously to investigate the role of CD48 In cell mediated immunity in vivo. Antl-CD48 mAb diminished the contact sensitivity response to the hapten trlnltrophenol (TNP). mAb also inhibited in vivo priming for the subsequent generation of secondary, TNP-speclflc, cytotoxic T lymphocytes (CTL) in vitro. The inhibitory effect was most effective in the afferent or inductive phase of immunity for CTL, while antl-CD48 mAb was most inhibitory for the efferent or ellcltatlve phase of contact sensitivity. Addition of antl-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 untreated animals showed no evidence for suppressor cells. Further experiments revealed that mAb administered in vivo, as well as to culture, Inhibited development of primary, alloantlgen-speclflc CTL in vitro. Mixed lymphocyte reaction and phytohemagglutlnln proliferation were partially suppressed by mAb administered in vivo or in vitro, whereas other mltogenlc responses remained unaffected. Flow cytometrlc analysis revealed 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 subsequent responses to primary and secondary antlgenlc challenge.

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