Regulatory role of microfilaments in the induction of T4 cell proliferation and interleukin 2 production.
The role of microfilaments in human T4 cell proliferation and lymphokine production triggered via various pathways of activation was examined by investigating the effects of cytochalasins on these responses. The data demonstrate that the effects of cytochalasins vary depending on the nature of the stimulus and on the concentration of the cytochalasin. Concentrations of cytochalasin that would be expected to bind both the low and high affinity binding sites (5-20 microM), that represent cytosolic and surface actin filaments, respectively inhibited T4 cell proliferation regardless of the stimulus. T4 cell proliferation stimulated by antigen-bearing APC or anti-CD3 was inhibited much more markedly than responses stimulated by ionomycin and PMA. In contrast, concentrations of cytochalasin expected to bind only high affinity binding sites (0.125-1 microM), represented by surface actin filaments, enhanced T4 cell proliferation and interleukin 2 production stimulated by mAb to CD2, CD3, or class I major histocompatibility complex (MHC) molecules, but not those induced by mAb to the T cell receptor, paraformaldehyde fixed, or viable antigen-bearing APC, allogeneic APC, or ionomycin and PMA. The enhancing effect of cytochalasins on responses stimulated by cross-linking class I MHC molecules was studied in detail. Enhancement of T4 cell proliferation induced in this manner required that cytochalasin B was present between 4 and 18 hr of culture, but not before or after. The data demonstrate that T cell microfilaments play a number of roles in determining the magnitude of T cell responses induced by engaging specific cell surface receptors and imply that different components of the microfilament system exert opposing intrinsic regulatory effects on T cell function.
Geppert
T D
TD
Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
Lipsky
P E
PE
D008841:Actin Cytoskeleton / Q000502:physiology*; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000941:Antigens / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003571:Cytochalasin B / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008934:Mitogens; D010703:Phorbol Esters / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell
D000911:Antibodies, Monoclonal; D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D008934:Mitogens; D010703:Phorbol Esters; D011948:Receptors, Antigen, T-Cell; D015638:Cytochalasin D; D003571:Cytochalasin B; D015759:Ionomycin