A helper T cell clone produces an antigen-specific molecule (T-ABM) which functions in the induction of suppression.
Among Ly-1+,2-T cells there appears to be two independent modes of antigen recognition. Helper and cytotoxic Ly-1 T cells recognize antigen only in the context of I region products whereas regulatory T cells, such as T suppressor inducer cells, produce antigen-specific, antigen-binding molecules (T-ABM). These T-ABM often have been found to form a part of biologically active, antigen-specific regulatory factors. A number of environmental conditions effect whether a foreign antigen will produce a positive response leading to immunity or a negative one leading to tolerance. Many of the conditions which favor the induction of suppressor T cells simultaneously preclude the proper interaction of antigen presenting cells with helper T cells. This parallel led us to ask whether helper T cells perform at least two, apparently opposite functions: a) under conditions favoring immunity helper T cells produce lymphokines to activate immune effector cells, and b) under conditions favoring suppression they produce molecules which function in suppressor cell induction. Therefore, this question relates to the mechanisms by which an immune response is switched into either a positive (help) or negative (suppressive) track. In addition, it begins to address the relationship between the different modes of antigen recognition exhibited by helper T cells vs. T suppressor inducer cells (see above). To explore this problem we employed an antigen-specific, I-Ak restricted helper T cell clone as the purest available source of helper T cells. We presented antigen to the cloned T cells under conditions which favor suppression rather than help (for example, by ultraviolet irradiation of the antigen-presenting cells) and collected supernatants 48 hrs later. The supernatants were then examined for activity in a functional assay for antigen-specific suppressor factors. Our results indicate that under conditions favoring suppression, a T-ABM was produced which functioned in the antigen-specific induction of suppression in vitro. The T-ABM had the same antigen specificity as that exhibited by the helper T cell and was therefore probably derived from the clone. This observation introduces the possibility that the interaction between antigen-presenting cells and helper T cells is a crucial decision point in the immune response which can lead to either immunity or suppression. The latter would be achieved through the production, by helper T cells, of an antigen-specific component of T suppressor inducer factor (i.e., the T-ABM). The possible relationship between T-ABMs and the T cell receptor is discussed.
Green
D R
DR
Department of Pathology, Yale University School of Medicine, New Haven, CT.
Chue
B
B
Zheng
H G
HG
Ferguson
T A
TA
Beaman
K D
KD
Flood
P M
PM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000528:radiation effects; D000941:Antigens; D000950:Antigens, Ly; D002999:Clone Cells / Q000276:immunology; D003207:Conalbumin / Q000276:immunology; D000949:Histocompatibility Antigens Class II; D007108:Immune Tolerance; D051379:Mice; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000941:Antigens; D000950:Antigens, Ly; D000949:Histocompatibility Antigens Class II; C043911:I-J-antigen; D013491:Suppressor Factors, Immunologic; D003207:Conalbumin