Normal hematopoiesis is maintained by activated bone marrow CD4+ T cells.
CD4(+) T cells produce hematopoietic-related cytokines and are essential for hematopoiesis stimulation during infection and hematologic recovery after bone marrow transplantation. However, it remains unclear if T cells are necessary to maintain normal hematopoiesis. We report here that, in T-cell-deficient mice, terminal differentiation of myeloid progenitors is defective, resulting in very low levels of granulocytes in the periphery. Hematopoiesis is restored after thymus graft or reconstitution with CD4(+) T cells but not CD8(+) T cells. Bone marrow CD4(+) T cells have an activated phenotype and produce cytokines, apparently, in the absence of exogenous stimulation. Transgenic mice carrying T-cell receptor specific for an ovalbumin peptide presented in the context of a specific class II molecule (I-A(d)) (DO11.10 RAG(-/-)) show the same hematopoietic deficiency as athymic mice. Their bone marrow CD4(+) T cells are not activated, suggesting that hematopoiesis maintenance requires the presence of cognate antigen in order to activate bone marrow T-helper cells. In fact, priming of transgenic mice with ovalbumin restores normal hematopoiesis. The data show that the current concept of "normal hematopoiesis" does not reflect a basal bone marrow activity, but it is an antigen-induced state maintained by constant activation of bone marrow CD4(+) T cells.
Monteiro
João P
JP
Divisão de Medicina Experimental, Coordenação de Pesquisa, Instituto Nacional de Câncer, Brazil.
Benjamin
Aline
A
Costa
Elaine S
ES
Barcinski
Marcello A
MA
Bonomo
Adriana
A
D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002478:Cells, Cultured; D018920:Coculture Techniques; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology*; D007275:Injections, Intravenous; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D016513:Mice, SCID; D008822:Mice, Transgenic; D038042:Myelopoiesis / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000637:transplantation
D000941:Antigens; D010047:Ovalbumin