Development of Th1-type immune responses requires the type I cytokine receptor TCCR

On antigen challenge, T-helper cells differentiate into two functionally di stinct subsets, Th1 and Th2, characterized by the different effector cytoki nes that they secrete(1). Th1 cells produce interleukin (IL)-2, interferon- gamma (IFN-gamma) and lymphotoxin-beta, which mediate pro-inflammatory func tions critical for the development of cell-mediated immune responses, where as Th2 cells secrete cytokines such as IL-4, IL-5 and IL-10 that enhance hu moral immunity(1,2). This process of T-helper cell differentiation is tight ly regulated by cytokines. Here we report a new member of the type I cytoki ne receptor family, designated T-cell cytokine receptor (TCCR). When challe nged in vivo with protein antigen, TCCR-deficient mice had impaired Th1 res ponse as measured by IFN-gamma production. TCCR-deficient mice also had inc reased susceptibility to infection with an intracellular pathogen, Listeria monocytogenes. In addition, levels of antigen-specific immunoglobulin-gamm a 2a, which are dependent on Th1 cells, were markedly reduced in these mice . Our results demonstrate the existence of a new cytokine receptor involved in regulating the adaptive immune response and critical to the generation of a Th1 response.