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Cutting edge: CD4 is not required for the functional activity of IL-16

N L Mathy1, N Bannert, S G Norley

  • 1Paul-Ehrlich Institute, Langen, Germany. matna@pei.de

Journal of Immunology (Baltimore, Md. : 1950)
|April 26, 2000
PubMed

Insights

Interleukin-16 (IL-16) does not require CD4 for its functions, including cell attraction and cytokine induction. This study found CD4 knockout cells respond normally to IL-16, challenging previous assumptions.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Interleukin-16 (IL-16) is a cytokine with known roles in immune cell chemotaxis, HIV replication inhibition, and pro-inflammatory cytokine induction.
  • Previous research suggested CD4 as the IL-16 receptor due to CD4+ cell responsiveness and blocking effects of anti-CD4 antibodies and soluble CD4.
  • Direct evidence for CD4 as the IL-16 receptor has been lacking.

Purpose of the Study:

  • To investigate the requirement of CD4 for IL-16's biological functions.
  • To determine if CD4 is the primary receptor for IL-16.
  • To clarify the interaction between IL-16 and CD4.

Main Methods:

  • Utilized CD4 knockout mice and their wild-type equivalents.
  • Assessed IL-16-mediated chemotaxis in CD4 knockout and wild-type cells.
  • Measured IL-16-induced production of pro-inflammatory cytokines in both cell types.
  • Evaluated the inhibitory effect of soluble CD4 on IL-16 function in CD4 knockout and wild-type cells.

Main Results:

  • Cells from CD4 knockout mice exhibited normal responsiveness to IL-16 in chemotaxis assays.
  • CD4 knockout cells showed typical induction of pro-inflammatory cytokines upon IL-16 stimulation.
  • The inhibitory effect of soluble CD4 on IL-16 function was absent in CD4 knockout cells, unlike in wild-type cells.

Conclusions:

  • CD4 is not essential for the chemotactic and cytokine-inducing functions of IL-16.
  • These findings challenge the established notion of CD4 as the major IL-16 receptor.
  • Suggests an alternative molecule likely acts as the primary receptor for IL-16.

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