{'fraction_non_alphanumeric': 0.0262551819438047, 'fraction_numerical': 0.02487333026255182, 'mean_word_length': 5.2956521739130435, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Signal transduction through cd4 receptors: stimulatory vs. inhibitory activity is regulated by cd4 proximity to the cd31t cell receptor

The binding of antibody to the CD4 molecule inhibits mobilization of cytoplasmic free calcium ([Ca2+]i) in response to CD3 cross‐linking on resting T cells. Similarly, when CD3 and CD4 are independently and simultaneously cross‐linked, calcium mobilization is inhibited when compared to that induced by cross‐linking CD3 alone. In contrast, when anti‐CD4 and anti‐CD3 are cross‐linked together, calcium mobilization is substantially higher than from CD3 cross‐linking alone. A heteroconjugate consisting of covalently bound CD3 and CD4 monoclonal antibodies (mAb) retains the ability to mobilize [Ca2+]i in CD4 cells at protein concentrations approximately two orders of magnitude lower than the free CD3 mAb, and the activity of the heteroconjugate is inhibitable by free CD4 mAb. The CD3/CD4 heteroconjugate also shows significantly greater activity in stimulation of inositol phosphate IP1, IP2 and IP3 synthesis in T cells than the CD3 mAb alone, and again the activity is inhibited by free CD4 mAb. The activity of the CD3/CD4 heteroconjugate is not simply due to oligomerization, since CD3/CD3 or CD4/CD4 homoconjugates or homoconjugate mixtures did not show increased activity. Other heteroconjugates (CD3/CD5 and CD3/CD28) were not different than the CD3/CD3 homoconjugate in their ability to increase [Ca2+]i. Purified CD4 T cells that do not respond to CD3 mAb in solution do respond to the CD3/CD4 heteroconjugate in solution by proliferating in the presence of a CD28 mAb, with a significant fraction of CD4 cells entering the second cycle within the first three days of stimulation. The CD3/CD4 heteroconjugate co‐modulates the CD3 and CD4 receptors, indicating that the heteroconjugate is not simply anchoring the T cell receptor to the T cell surface like anti‐CD3 on a solid surface. These results suggest that CD4 plays an active role in signal transduction when brought into close physical proximity to the CD3/T cell receptor complex during major histocompatibility complex class II‐restricted antigen presentation.