Endogenous production of prothymocyte differentiating activity by phytohemagglutinin-stimulated T-cell-depleted human marrow.
The PHA responsiveness of marrow T-cell precursors remains a matter of controversy. We have investigated the capacity of human marrow to proliferate under phytohemagglutinin (PHA) stimulation following extensive removal of mature T cells by complement-dependent cytotoxicity with MBG6 and RFT8 monoclonal antibodies. PHA-induced thymidine uptake by marrow cells occurred with a peak on Days 6-8 of incubation instead of Day 3 for PBL. This peak was observed 48 hr earlier in the presence of PHA-stimulated T-depleted marrow cell supernatants. These supernatants can also promote the growth of mature T-cell colonies from MBG6-, RFT8-, T11-, T3- marrow. However, full colony development requires exogenous interleukin 2 (IL-2). IL-2 could be detected in marrow supernatants but only at very low levels and beyond Days 3 and 4. In contrast Days 1-6 marrow supernatants were equally effective in promoting MBG6-RFT8- marrow cell responsiveness to PHA. We conclude that marrow T-cell precursors are not PHA responsive and that PHA induces the production by marrow non-T cells of a prothymocyte-differentiating activity (PTDA); PTDA can differentiate marrow T-cell progenitors into PHA-responsive T cells; following activation by PHA, these cells undergo limited proliferation induced by IL-2 endogenously released from de novo differentiated T cells. It is suggested that this mechanism may account for extrathymic differentiation of the T-cell lineage in heavily irradiated marrow transplantation recipients.
D000911:Antibodies, Monoclonal / Q000276:immunology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D008213:Lymphocyte Activation; D010641:Phenotype; D010835:Phytohemagglutinins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology*
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D007376:Interleukin-2; D010835:Phytohemagglutinins