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CD4 ligand IL-16 inhibits the mixed lymphocyte reaction.

A C Theodore, D M Center, J Nicoll, G Fine, H Kornfeld and W W Cruikshank
J Immunol September 1, 1996, 157 (5) 1958-1964;
A C Theodore
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D M Center
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J Nicoll
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G Fine
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H Kornfeld
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W W Cruikshank
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Abstract

CD4 participation in TCR/CD3-associated activation through interaction with the MHC class II Ags results in formation of a CD4-TCR/CD3 complex capable of maximal signal transduction. When CD4 binds to alternative ligands such as HIV-1 gp120 or anti-CD4 Abs, Ag stimulation of TCR/CD3 is markedly inhibited, and an unresponsive state develops. To determine if the natural CD4 ligand interleukin-16 also induces unresponsiveness, we tested the effects of rIL-16 on T cell proliferation in mixed lymphocyte reactions. rIL-16 suppressed T cell proliferation in a dose-dependent manner at concentrations of 10(-11) to 10(-7) M. Inhibition of proliferation was present on days 5 to 9 of the mixed lymphocyte reaction. rIL-16 did not modulate membrane CD4, significantly change basal [3H]thymidine incorporation in resting T lymphocytes, or alter viability. The suppressive effect was specifically blocked by preincubation with neutralizing anti-rIL-16 mAb or with recombinant soluble CD4. While the expression of IL-2R on responder cells was unaffected by rIL-16, the addition of exogenous rIL-2 did not restore T cell responsiveness. The unresponsiveness induced by rIL-16 is distinct from that of other CD4 ligands in that CD4 and IL-2R expression are unaffected. The failure of rIL-2 to restore proliferation suggests that the decrease in T cell responsiveness induced by rIL-16 may result from an interruption in the IL-2R-signaling mechanism. These results may help explain how CD4 delivers both activating and inhibitory signals and provides a rationale for the role of IL-16 in the regulation of immune responses.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 157, Issue 5
1 Sep 1996
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CD4 ligand IL-16 inhibits the mixed lymphocyte reaction.
A C Theodore, D M Center, J Nicoll, G Fine, H Kornfeld, W W Cruikshank
The Journal of Immunology September 1, 1996, 157 (5) 1958-1964;

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CD4 ligand IL-16 inhibits the mixed lymphocyte reaction.
A C Theodore, D M Center, J Nicoll, G Fine, H Kornfeld, W W Cruikshank
The Journal of Immunology September 1, 1996, 157 (5) 1958-1964;
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Print ISSN 0022-1767        Online ISSN 1550-6606