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J. Exp. Med.,
Volume 188, Number 7, October 5, 1998 1211-1221
By
From the Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston,
Texas 77030
Scrape loading Clostridium botulinum C3 exoenzyme into primary peripheral blood human T
lymphocytes (PB T cells) efficiently adenosine diphosphate (ADP)-ribosylates and thus inactivates the guanosine triphosphatase (GTPase) Rho. Basal adhesion of PB T cells to the 
1 integrin substrate fibronectin (Fn) was not inhibited by inactivation of Rho, nor was upregulation
of adhesion using phorbol myristate acetate (PMA; 10 ng/ml) or Mn++ (1 mM) affected.
Whereas untreated PB T cells adherent to Fn remain spherical, C3-treated PB T cells extend
F-actin-containing pseudopodia. Inactivation of Rho delayed the kinetics of PMA-dependent PB T cell homotypic aggregation, a process involving integrin 
L2. Although C3 treatment
of PB T cells did not prevent adhesion to the 1 integrin substrate Fn, it did inhibit 1 integrin/CD3-mediated costimulation of proliferation. Analysis of intracellular cytokine production at the single cell level demonstrated that ADP-ribosylation of Rho inhibited 1 integrin/
CD3 and CD28/CD3 costimulation of IL-2 production within 6 h of activation. Strikingly,
IL-2 production induced by PMA and ionomycin was unaffected by C3 treatment. Thus, the
GTPase Rho is a novel regulator of T lymphocyte cytoarchitecture, and functional Rho is required for very early events regulating costimulation of IL-2 production in PB T cells.
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