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PMID: 1682413 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Anti-CD2 antibodies induce T cell unresponsiveness in vivo.

The Journal of experimental medicine ·Vol. 174 ·No. 5 ·1991-11-01 ·Pages 957-67

Gückel B, Berek C, Lutz M, Altevogt P, Schirrmacher V, Kyewski BA

Abstract

The CD2 receptor functions as an adhesion and signal molecule in T cell recognition. Multimeric binding of CD2 on T cells to its physiologic ligand LFA-3 on cognate partner cells in vitro efficiently augments the antigen-specific T cell signal delivered by the T cell receptor/CD3 complex. The precise contribution of the antigen-nonspecific CD2-LFA-3 interactions to T cell immune responses in vivo, however, has been difficult to assess. Here we analyzed the role of CD2 in the murine immune response using a nondepleting anti-CD2 monoclonal antibody that induces a marked, reversible modulation of CD2 expression on murine T and B cells in situ. This modulation is dose and time dependent, specific for CD2, and does not require the Fc portion of the antibody. Anti-CD2 antibodies [rat IgG1 or F(ab')2] significantly inhibit the CD4+ T cell-mediated response to hen egg lysozyme and the cytotoxic CD8+ T cell response to a syngeneic tumor cell line. In both cases, anti-CD2 antibodies are only effective when administered before or within 24 h after antigen priming. The suppression of the antitumor response corresponds to a sixfold reduction of specific cytotoxic T lymphocyte precursor cells and results in the abrogation of protective antitumor immunity. Anti-CD2 antibodies also affect the humoral immune response to oxazolone: the isotype switch from specific IgM to IgG1 antibodies is delayed, whereas the IgM response is unaltered. In addition, a single antibody injection results in sustained polyclonal unresponsiveness of T cells irrespective of antigen priming and CD2 modulation. These results document that CD2-mediated signals induce a state of T cell unresponsiveness in vivo.

MeSH Terms
Animals Antibodies, Monoclonal/immunology Antibody Formation Antigens, Differentiation, T-Lymphocyte/analysis,immunology,physiology CD2 Antigens CD4 Antigens/analysis CD8 Antigens/analysis Mice Mice, Inbred C3H Mice, Inbred DBA Muramidase/immunology Receptors, Immunologic/analysis,immunology,physiology T-Lymphocytes/immunology T-Lymphocytes, Cytotoxic/immunology
Chemicals
Antibodies, Monoclonal Antigens, Differentiation, T-Lymphocyte CD2 Antigens CD4 Antigens CD8 Antigens Receptors, Immunologic Muramidase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Gückel B
Institute for Immunology and Genetics, German Cancer Research Center, Heidelberg.
Berek C
Lutz M
Altevogt P
Schirrmacher V
Kyewski B A
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.174.5.957
Published
1991-11-01
Pages
957-67
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118978
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.174.5.957 PMC Full Text View journal details
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