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Interleukin-2 in vivo: production of and response to interleukin-2 in lymphoid organs undergoing a primary immune response to heterologous erythrocytes.

In this report, we describe experiments which demonstrate that antigenic stimulation in vivo causes the appearance of cells in both spleen and lymph node which secrete interleukin-2 (IL-2). Cells also appear in these organs which proliferate in response to IL-2. For these experiments, sheep red cells (SRBC) were injected into the spleens or footpads of mice, and cell suspensions from spleens or popliteal lymph nodes prepared at various times after antigenic stimulation. These cells were assayed for their ability to respond to IL-2, and their cell culture supernatants for secreted IL-2. The proliferative response to IL-2 steadily increased following SRBC injection to reach a peak at Day 2 for spleen cells and at Day 3 for lymph node cells. Maximal production of IL-2 was displaced from the maximal response to the lymphokine by peaking one day later for both organs. Our results strongly implicate the participation of IL-2 in the in vivo immune response and suggest the existence of in vivo regulatory mechanisms, which can control the time of IL-2 production and also the appearance of cells with receptors for IL-2.