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The Journal of Immunology, Vol 138, Issue 3 795-801, Copyright © 1987 by American Association of Immunologists

ARTICLES

The role of interleukin 2 in inducing Ig production in a pokeweed mitogen-stimulated mononuclear cell system

N Nakagawa, T Nakagawa, DJ Volkman, JL Ambrus Jr and AS Fauci

Cyclosporin A (CsA) has been found previously to block mitogen- stimulated T cell proliferation and production of discrete T cell- derived lymphokines such as interleukin 2 (IL 2) and interferon (IFN)- gamma. In addition, CsA blocks pokeweed mitogen (PWM)-driven T cell- dependent differentiation of B cells into immunoglobulin (Ig)-secreting cells. Recently, we reported that CsA (1 microgram/ml) inhibited PWM- induced T cell production of IL 2 and IFN-gamma, but supernatants retained B cell differentiation factor (BCDF)-like activity. The present study demonstrates the ability of CsA to suppress T cell functions in PWM-driven Ig production in mononuclear cells (MNC), and the capacity of exogenous T cell lymphokines to reverse CsA-induced suppression. CsA profoundly suppressed PWM-driven PFC formation (greater than 95%). However, Ig production was substantially reconstituted by the addition of IL 2 at concentrations of 10 to 50 U/ml. In contrast, no effects were observed by the addition of IFN- gamma or BCGF. The kinetics of CsA inhibition of Ig production and IL 2 secretion were found to be closely related. In addition, to obtain effective reconstitution in the CsA-treated PWM-MNC system it was necessary to add IL 2 at the initiation of culture. T cells themselves were also required for B cell differentiation in this system. However, surface Ig+ cells obtained by cell sorting after 3 days of culture could differentiate in the absence of T cells but only in response to IL 2, not in response to IFN-gamma or BCDF. Thus, in PWM-driven B cell differentiation T cells are necessary early in culture, whereas IL 2 is essential from the initial stage of B cell activation through the final stage of B cell differentiation.


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