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 ligand LFA-3 (CD58) and as a ligand itself for murine CD2, the anti-murine CD48 mAb HM48-1 was administered intravenously to investigate the role of CD48 in cell mediated immunity in vivo. Anti-CD48 mAb diminished 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 inhibitory 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 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, alloantigen-specific CTL in vitro. Mixed lymphocyte reaction and phytohemagglutinin proliferation were partially suppressed by mAb administered in vivo or in vitro, whereas other mitogenic responses remained unaffected. Flow cytometric 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Chavin
K D
KD
Department of Surgery, Medical University of South Carolina, Charleston 29425.
Qin
L
L
Lin
J
J
Woodward
J
J
Baliga
P
P
Kato
K
K
Yagita
H
H
Bromberg
J S
JS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018801:CD2 Antigens; D000071178:CD48 Antigen; D018968:CD58 Antigens; D003260:Contact Inhibition; D003602:Cytotoxicity, Immunologic; D005260:Female; D007111:Immunity, Cellular; D007275:Injections, Intravenous; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D018968:CD58 Antigens; C000604066:Cd48 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic