TRENDS
Suppressor T cells: some answers but more
questions Martin E. Dorf, Vijay K. Kuchroo and Mary Collins
The concept that suppressor T (T s) cells play an important role in regulating immune responses has been challenged over the past several years. However, it is clear that, although clonal deletion plays a major role in the development of tolerance to self antigens, mechanisms of peripheral tolerance exist. Both suppression and anergy have been postulated to fulfill this role. Although anergic T cells can be identified in the periphery, the anergy model does not account for the findings that adoptive transfer of T cells from mice tolerant to a given antigen reduces the immune response to that same antigen in syngeneic recipients. The best explanation for this result is thatT cells exist that can suppress immune responses. It has been difficult to characterize T s cells and the factors made by T s hybridomas that substitute for T s cells. However, progress has been achieved on several points, including the definition of (1) the requirements for induction of T s cell activity, (2) the relationship between T s cell receptors and the antigen-binding factors released by T s hybridomas (TsFs), (3)the specificity o f T s cell responses, and (4) effector mechanisms. Induction of T s cells Requirements for the induction of T s cells are distinct from those for the induction of helper (TH) cells. Tenfold fewer antigen-presenting cells (APCs) are required for the induction of T s than T H cells. The most efficient APC in inducing T s cells is the macrophage; such macrophages are operationally distinguished from those which induce T H cells by the criteria of ultraviolet (UV) and cyclophosphamide sensitivity I. The mechanisms whereby these treat-
Many properties of suppressor T cells and the antigen-bindingfactors derived from them have evaded molecular genetic definition. Here, Martin Dorf and colleagues discuss recent data in the context of a growing awareness of the and 1-E. A recombinational hotspot was located within the E13 gene but molecules and principles involved. ments affect APC function are unclear but may involve interference with costimulatory molecules or cytokine production 2. Major histocompatibility complex (MHC) class 11 molecule expression on APCs is necessary for T~ cell induction, and gamma-interferon (IFN-y), which induces expression of MHC class II, enhances the capacity of macrophages to generate T s cells. Induction of T H and T s cell responses can be mediated by the same MHC class-II-bearing macrophage cloned cell lines
Suppressor T cells: some answers but more
questions Martin E. Dorf, Vijay K. Kuchroo and Mary Collins
The concept that suppressor T (T s) cells play an important role in regulating immune responses has been challenged over the past several years. However, it is clear that, although clonal deletion plays a major role in the development of tolerance to self antigens, mechanisms of peripheral tolerance exist. Both suppression and anergy have been postulated to fulfill this role. Although anergic T cells can be identified in the periphery, the anergy model does not account for the findings that adoptive transfer of T cells from mice tolerant to a given antigen reduces the immune response to that same antigen in syngeneic recipients. The best explanation for this result is thatT cells exist that can suppress immune responses. It has been difficult to characterize T s cells and the factors made by T s hybridomas that substitute for T s cells. However, progress has been achieved on several points, including the definition of (1) the requirements for induction of T s cell activity, (2) the relationship between T s cell receptors and the antigen-binding factors released by T s hybridomas (TsFs), (3)the specificity o f T s cell responses, and (4) effector mechanisms. Induction of T s cells Requirements for the induction of T s cells are distinct from those for the induction of helper (TH) cells. Tenfold fewer antigen-presenting cells (APCs) are required for the induction of T s than T H cells. The most efficient APC in inducing T s cells is the macrophage; such macrophages are operationally distinguished from those which induce T H cells by the criteria of ultraviolet (UV) and cyclophosphamide sensitivity I. The mechanisms whereby these treat-
Many properties of suppressor T cells and the antigen-bindingfactors derived from them have evaded molecular genetic definition. Here, Martin Dorf and colleagues discuss recent data in the context of a growing awareness of the and 1-E. A recombinational hotspot was located within the E13 gene but molecules and principles involved. ments affect APC function are unclear but may involve interference with costimulatory molecules or cytokine production 2. Major histocompatibility complex (MHC) class 11 molecule expression on APCs is necessary for T~ cell induction, and gamma-interferon (IFN-y), which induces expression of MHC class II, enhances the capacity of macrophages to generate T s cells. Induction of T H and T s cell responses can be mediated by the same MHC class-II-bearing macrophage cloned cell lines
