Proliferation of peripheral lymphocytes to interleukin-2 and interleukin-4 after marrow transplantation.

Defects in the interleukin-2 (IL-2)-mediated T-lymphocyte activation/proliferation pathway have been implicated as contributing to the compromised immune function observed in patients following bone marrow transplantation (BMT). Since interleukin-4 (IL-4) is also involved in T-lymphocyte function, we have examined whether phytohemagglutinin (PHA)- or anti-CD3 (OKT3)-activated lymphocytes obtained from patients after allogeneic or autologous BMT are capable of proliferating in response to human recombinant IL-4, and compared these results to those obtained using human recombinant IL-2. Peripheral blood lymphocytes from marrow graft recipients were initially cultured for 3 days in the presence of PHA or OKT3. Such mitogen-activated lymphocytes exhibited little or no proliferation (as assessed by incorporation of [3H]-thymidine) following culture for an additional 3 days in the presence of IL-4 or IL-2. Results were similar for lymphocytes obtained from patients early (less than 4 months) after marrow grafting and those obtained from long-term marrow graft recipients with chronic graft-vs-host disease at the time of testing. In contrast, lymphocytes obtained from healthy individuals proliferated in response to IL-4, as well as to IL-2, following initial activation with PHA or OKT3. Immunofluorescence analysis showed that in normals equal numbers of CD4 and CD8 cells proliferated after stimulation with anti-CD3 antibody and IL-2. However, in BMT patients there was a predominant proliferation of CD8 cells using the same stimulator. These results indicate that defects in the IL-4-mediated T-lymphocyte activation/proliferation pathway may also contribute to the immunodeficiency observed following BMT.