REVISITING THE TH1 TH2 PARADIGM

The identification of subsets of CD4(+) helper cells producing distinc t pattern of cytokines has provided a valuable framework for understan ding how different effector populations of immune cells can be recruit ed in vivo during infection. In the view of most investigators, Th1 an d Th2 cells produce factors that serve as their own autocrine factors and cytokines exerting suppressive activities on each other's developm ent and activity. This concept intuitively explains the natural tenden cy of immune responses to become progressively polarized. However, sev eral experimental observations appear difficult to rationalize with a simple, 'symmetrical' Th1/Th2 paradigm including those that Th1 cells do not produce their own growth factor; that both Th1 and Th2 cells ca n promote inflammatory responses; that interleukin-10 (IL-10) inhibits inflammatory responses in a Th1/Th2-independent fashion; that IL-10 p romotes the development of Th1-type effector cells; and that IL-12 can amplify pre-established Th2 responses. The purpose of the present ana lysis is to provide a revised model for better understanding how cytok ines regulate immune responses in vivo.