T(H)1 AND T(H)2 HELP FOR B-CELLS - DIFFERENTIAL CAPACITY FOR INDUCTION OF AUTONOMOUS RESPONSIVENESS TO IL-2

Sustained interaction with T(h)1. cells has been shown to induce IL-2 responsiveness by murine a cells. This is equivalently dependent on CD 40, CD54/ICAM-1 and MHC II ligation, and co-crosslinking of CD54 and M HC II in the presence of IL-5 up-regulates a functional IL-2R on a cel ls. We now show that IL-5 (125 U/ml) synergizes with T(h)1 cells to in duce a cell responses to IL-2, that are maintained following T-cell re moval, e.g. autonomous. T(h)1 help in the absence of IL-5 resulted in weak or undetectable responses following T cell removal. The mechanism of IL-5 synergy involved persistence of IL-SRP expression following T cell removal, as opposed to enhancement of IL-2R induction or functio n. The level of contact-induced IL-2R expression on a cells was not it self modified by IL-5. The effects of IL-5 did not overcome the requir ement for T contact signals and treatment of a cells with soluble anti -Ig did not circumvent the need for IL-5 for autonomous IL-2 responses . Consistent with the above, interaction with an IL-5-producing T(h)2 clone induced strong autonomous a cell responses to IL-2. Qualitative differences of T(h)2 help over that of T(h)1 may thus be attributable to their differential ability to induce autonomous a cell responsivene ss to cytokines. This may be representative of events in which mainten ance of cell cycle is important, as is the case in germinal centers.