Differential effect of cholera toxin on CD45RA + and CD45RO + T cells: specific inhibition of cytokine production but not proliferation of human naive T cells

We have studied how cholera toxin (CT) and its non‐toxic cell‐binding B‐subunit (CTB) affect the activation of pure human T cells in an anti‐CD3‐driven system. CT, as opposed to CTB, strongly suppressed the proliferative responses as well as cytokine production in CD4 + and CD8 + T cells. CT however, had a differential effect on naive and activated/memory T cell subsets. Costimulation through exogenous IL‐2 or through CD28 cross‐linking rescued the proliferation of CT‐treated naive CD45RA + T cells, but not of activated/memory CD45RO + cells. IL‐2 production and IL‐2 receptor expression were markedly reduced by CT in all T cell fractions, i.e. also in CD45RA + cells which had maintained proliferative responses. However, the proliferative responses of CT‐treated CD45RA + T cells were IL‐2‐dependent, as shown by blocking experiments using anti‐IL‐2 antibodies. These results indicate (i) that CTB has no cytostatic effect on human T cells, (ii) that CT affects proliferation and cytokine production by two different signal pathways, and (iii) that CT might interact with a signal pathway generated through or influenced by CD45.