Purified Human T Cells Stimulated with Cross-Linked Anti-CD3 Monoclonal Antibody OKT3: rIL-1 is a Co-Stimulatory Factor for CD4+ CD29+ CD45RA- T Cells

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Abstract
Accessory cells (AC) are believed to play two major roles in T‐cell activation: they cross‐link certain stimuli such as monoclonal antibodies, and they provide needed cytokines. To differentiate between these roles, we cross‐linked OKT3 on highly purified T‐cells by means of Fc‐specific goat anti‐mouse IgG‐coated polystyrene heads and studied T‐cell activation after exogenously added cytokines. Following addition of AC, rIL‐2. or rIL‐1. CD25 was up‐regulated, and the cells proliferated and became cytotoxic. Both CD4+ and CD8+ cells were activated in the presence of AC or rIL‐2. In contrast, only CD4+ CD29+ CD4SRA cells responded in the presence of rIL‐1. Anti‐IL‐2R p55 (anti‐TAC) monoclonal antibody inhibited the proliferative response supported by rIL‐2 or rIL‐1. To inhibit proliferation of cells stimulated in the presence of AC. anti‐TAC needed to be supplemented with anti‐IL‐6 antibodies, or to be added in a 10‐fold higher concentration. Cultures with AC produced larger amounts of IL‐2 than those supplemented with rIL‐1. Only AC‐containing cultures also produced detectable amounts of IL‐6. These findings combined with the observation that none of 2000 purified T cells counted in each of six independent experiments expressed MHC class II antigens strongly suggest that rIL‐I can activate T cells directly, rather than indirectly by potentiating the function of contaminating AC.