Regulation of tumor necrosis factor (TNF)‐α synthesis and TNF receptors expression in T lymphocytes through the CD2 activation pathway

The involvement of the CD2 (T11) molecule, an alternative activation pathway for T lymphocytes, in the regulation of tumor necrosis factor (TNF)‐α/TNF receptor system in human T lymphocytes has been investigated. It has been found that both TNF‐α synthesis and secretion were induced after incubation of purified T lymphocytes with the appropriate mitogenic combination of antibodies specific for two different epitopes on the CD2 molecule. Moreover, TNF‐α secretion was also observed by activation of T lymphocytes either through CD3 or CD69 molecular pathways, or with other stimulating agents such as Ca2+ ionophore in combination with phorbol esters. The expression of TNF receptors has been studied in both nonactivated and CD2‐activated T lymphocytes. Unstimulated T cells weakly expressed a functional 75‐kDa receptor form, whereas they lacked detectable levels of the 55‐kDa receptor form. Triggering of T cell activation through the CD2 molecule also markedly increased the expression of the p75‐kDa TNF receptor form, but did not exert any inductive effect on the expression of the p55‐kDa TNF receptor. In addition, we have found that TNF‐α enhanced the proliferative response triggered by the mixture of anti‐CD2 monoclonal antibodies. Taken together, these results support a role for the CD2 activation pathway in the functional regulation of TNF‐α/TNF receptor system in T lymphocytes, and reinforce the view of CD2 as an alternative pathway for regulation of the cytokine network that modulates the function of T lymphocytes.