Bone marrow CD8 cells down-modulate membrane IL-7Ralpha expression and exhibit increased STAT-5 and p38 MAPK phosphorylation in the organ environment.
By comparing mature CD8-cell turnover in different organs, we previously demonstrated that CD8 cells proliferate predominantly in the bone marrow (BM). To investigate the mechanisms underlying such increased turnover, we compared BM, lymph nodes, and spleen CD8 cells from untreated C57BL/6 mice regarding in vivo proliferation within the organ; in vitro response to interleukin-7 (IL-7), IL-15, IL-21; ex vivo expression of membrane CD127 (IL-7Ralpha), intracellular Bcl-2, phospho-STAT-5 (signal transducer and activator of transcription 5), phospho-p38 mitogen activated protein kinase (MAPK); and in vivo proliferation on adoptive transfer. In the BM, the proliferation rate was increased for either total CD8 cells or individual CD44 and CD122 subsets. In contrast, purified CD8(+) cells from the BM did not show an enhanced in vitro proliferative response to IL-7, IL-15, and IL-21 compared with corresponding spleen cells. After transfer and polyinosinic-polycytidylic acid (polyI:C) treatment, both spleen-derived and BM-derived CD8 cells from congenic donors proliferated approximately twice more in the recipient BM than in spleen and lymph nodes. Our results suggest that BM CD8 cells are not committed to self-renewal, but rather are stimulated in the organ. Molecular events constantly induced in the CD8 cells within the BM of untreated mice include increase of both phosphorylated STAT-5 and phosphorylated p38 intracellular levels, and the reduction of CD127 membrane expression.
Cassese
Giuliana
G
Institute of Genetics and Biophysics Adriano Buzzati-Traverso, Consiglio Nazionale delle Ricerche, Naples, Italy.
Parretta
Elisabetta
E
Pisapia
Laura
L
Santoni
Angela
A
Guardiola
John
J
Di Rosa
Francesca
F
D019264:Adoptive Transfer; D000818:Animals; D001853:Bone Marrow / Q000254:growth & development / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes; D002462:Cell Membrane; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D007114:Immunization; D019409:Interleukin-15 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage; D010766:Phosphorylation / Q000187:drug effects; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000098546:Interleukin-21
D016827:CD8 Antigens; D019409:Interleukin-15; D015851:Interleukin-7; D007378:Interleukins; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; C415350:interleukin-7 receptor, alpha chain; D010047:Ovalbumin; D048051:p38 Mitogen-Activated Protein Kinases; D000098546:Interleukin-21