Cytokine synthesis and apoptosis by intestinal intraepithelial lymphocytes: Signaling of high density αβ T cell receptor+ and γδ T cell receptor+ T cells via T cell receptor-CD3 complex results in interferon-γ and interleukin-5 production,while low density T cells undergo DNA fragmentation

To study the biological consequences of cytokine production and apoptosis by intraepithelial lymphocytes (IEL), we have studied these characteristics in both the high and low density CD3⁺ IEL populations. Stimulation of low- or high-density CD3⁺ IEL via the T cell receptor (TCR)-CD3 complex using monoclonal anti-CD3, anti-αβ TCR or anti-γδ TCR antibodies resulted in opposing effects. In one case, a significant number of the high-density CD3⁺ T cells entered cell cycle from the resting stage (DNA replication was observed) and anti-TCR-CD3 treatment enhanced the numbers of interferon-γ and interleukin-5 spot-forming cells in this cell fraction. In contrast, when the low-density αβ TCR⁺ or γδ TCR⁺ T cells were activated via the TCR-CD3 complex, DNA fragmentation was observed. These results demonstrated that the activation signals transduced via the TCR-CD3 complex resulted in their entry into the cell cycle and subsequent interferon-γ and interleukin-5 production in the high-density IEL T cell subset. However, identical signals induced apoptosis in the majority of the low-density fraction of CD3⁺ IEL.