TUMOR-GROWTH CHANGES THE CONTRIBUTION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR DURING MACROPHAGE-MEDIATED SUPPRESSION OF ALLORECOGNITION

Tumor-bearing host (TBH) macrophages (MPHI) suppress T cell alloresponses, and this study suggests granulocyte-macrophage colony-stimulating factor (GM-CSF), a molecule associated with suppressive MPHI activity during tumor growth, signals more immunosuppression. In the absence of MPHI, GM-CSF increased T cell proliferation in response to alloantigen. However, TBH MPHI-mediated suppression of allorecognition was further induced by GM-CSF. Allogeneic mixed lymphocyte reaction (MLR) cultures, containing normal host (NH) MPHI, were either unaffected or enhanced. Prostaglandin E2 (PGE2), a highly suppressive monokine that decreases alloreactivity, did not seem to be involved in the suppression caused by the TBH MPHI/GM-CSF interaction. MPHI-CSF (M-CSF) addition to cultures did not reverse the suppression Caused by TBH MPHI and GM-CSF, and inhibition of PGE2 synthesis did not change the response to M-CSF. TBH Ia- MPHI, a suppressor population that predominates among splenic MPHI during tumor growth, demonstrated significantly lower reactivity in the presence of GM-CSF. In contrast, alloresponses suppressed by NH Ia- MPHI demonstrated higher reactivity in the presence of GM-CSF. The data collectively suggest that TBH MPHI respond differently to GM-CSF, and that tumor-induced changes in GM-CSF responsiveness affect MPHI accessory ability.