Signal requirements for the generation of T-lymphocytes from T-depleted bone marrow cells: a sequential study.
We have investigated the sequence of signals provided by a B- and null-cell-derived prothymocyte-differentiating activity (PTDA), phytohemagglutinin (PHA), and interleukin 2 (IL2) to the generation of mature T-lymphocytes by T-depleted bone marrow (BM) cells. Sequential studies show that preincubation of CD2-, CD3-, CD4-, CD6-, and CD8- BM cells with PTDA, but not with recombinant (r) IL2 or PHA increased their capacity to proliferate in liquid culture and to form agar T-cell colonies provided both PHA and rIL2 were added to the cultures. In contrast, the growth of T-cell-containing BM was significantly enhanced in both liquid and agar culture following its preincubation with rIL2 as well as with PTDA. The selective effect of PTDA on CD2-, CD3-, CD4-, CD6-, CD8- BM cells was abolished by adding a CD7 monoclonal antibody to the T-cell-purging coctail. Cell marker studies performed on T-cell-depleted BM-derived liquid or agar cultures have shown that they contain up to 70%-85% CD2+, CD3+, CD4+, CD8- cells. No IL1 or IL2 could substitute for PTDA, nor have these activities, as well as interferon (IFN), IL3, IL4, or granulocyte-macrophage colony-stimulating activity (GM-CSA) been detected so far in PTDA-containing preparations. These results indicate that PTDA can trigger marrow T-cell precursors into PHA-responsive T cells, which, following activation by PHA, require IL2 for growth. It is suggested that this may represent a thymus-independent alternative pathway for T-cell differentiation and activation.
Lecron
J C
JC
URA CNRS 1338, CHRU La Milétrie, Poitiers, France.
Mossalayi
M D
MD
Tanzer
J
J
Gomert
J
J
Goube de Laforest
P
P
D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000502:physiology; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000145:classification / Q000166:cytology*
D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D006133:Growth Substances; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011994:Recombinant Proteins