CD4 ligand IL-16 inhibits the mixed lymphocyte reaction.
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.
Theodore
A C
AC
The Pulmonary Center, Boston University School of Medicine, MA 02118, USA.
Center
D M
DM
Nicoll
J
J
Fine
G
G
Kornfeld
H
H
Cruikshank
W W
WW
D015704:CD4 Antigens / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019410:Interleukin-16 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007399:Interphase / Q000276:immunology; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008024:Ligands; D007959:Lymphocyte Culture Test, Mixed; D011994:Recombinant Proteins / Q000494:pharmacology
D015704:CD4 Antigens; D007166:Immunosuppressive Agents; D019410:Interleukin-16; D007376:Interleukin-2; D008024:Ligands; D011994:Recombinant Proteins; D004247:DNA