Effector memory T cells (T_EM) have an important role in immunity against infection. However, little is known about the factors regulating T_EM maintenance and proliferation. In this study, we investigated the role of direct interactions between CD4⁺ and CD8⁺ T cells (TC) for human T_EM expansion. Proliferation of separated or mixed CD4⁺ and CD8⁺T_EM populations was analyzed after polyclonal stimulation in vitro. Compared to each isolated subset mixed T_EM populations showed increased proliferation and expansion of both CD4⁺ and CD8⁺T_EM subpopulations. Combined activation of CD4⁺ and CD8⁺ memory T cells (Tmem) induced an increased expression of CD40L and CD40 on both populations. Subsequently, CD40/CD40L caused a bi‐directional stimulation of CD40⁺CD4⁺T_EM by CD40L⁺CD8⁺T_EM and of CD40⁺CD8⁺T_EM by CD40L⁺CD4⁺T_EM. Blocking of CD40L on activated CD8⁺T_EM selectively inhibited proliferation of CD4⁺T_EM, while blocking of CD40L on CD4⁺T_EM abrogated proliferation of CD8⁺T_EM. Taken together, we demonstrate for the first time that the expression of CD40L is exploited on the one hand by CD8⁺T_EM to increase the proliferation of activated CD4⁺T_EM and on the other hand by CD4⁺T_EM to support the expansion of activated CD8⁺T_EM. Thus, efficient T_EM expansion requires bi‐directional interactions between CD4⁺ and CD8⁺T_EM cells.