Comodulation of CXCR4 and CD26 in human lymphocytes

We provide convergent and multiple evidence for a CD26/CXCR4 interaction. T hus, CD26 codistributes with CXCR4, and both coimmunoprecipitate from membr anes of T (CD4(+)) and B (CD4(-)) cell lines. Upon induction with stromal c ell-derived factor 1 alpha (SDF-1 alpha), CD26 is cointernalized with CXCR4 . CXCR4-mediated downregulation of CD26 is not induced by antagonists or hu man immunodeficiency virus (HIV)-1 gp120. SDF-1 alpha -mediated down-regula tion of CD26 is not blocked by pertussis toxin but does not occur in cells expressing mutant CXCR4 receptors unable to internalize. Codistribution and cointernalization also occurs in peripheral blood lymphocytes. Since CD26 is a cell surface endopeptidase that has the capacity to cleave SDF-1 alpha , the CXCR4CD26 complex is likely a functional unit in which CD26 may direc tly modulate SDF-1 alpha -induced chemotaxis and antiviral capacity. CD26 a nchors adenosine deaminase (ADA) to the lymphocyte cell surface, and this i nteraction is blocked by HIV-1 gp120. Here we demonstrate that gp120 intera cts with CD26 and that gp120-mediated disruption of ADA/CD26 interaction is a consequence of a first interaction of gp120 with a domain different from the ADA binding site. SDF-1 alpha and gp120 induce the appearance of pseud opodia in which CD26 and CXCR4 colocalize and in which ADA is not present. The physical association of CXCR4 and CD26, direct or part of a supramolecu lar structure, suggests a role on the function of the immune system and the pathophysiology of HIV infection.