Cytokine regulation of early human lymphopoiesis.
An in vitro culture system in which bone marrow-derived fibroblast-like cells support the growth of TdT+ colonies derived from CD34+/CD10- human bone marrow progenitor cells has recently been described. The regulatory role of cytokines during early B lineage commitment was investigated using this culture system. Expression of IL-7, a cytokine that induces proliferation of B cell precursors, was detectable in the adherent layer by PCR and bioassay. Lymphoid progenitor colonies were inhibited by neutralizing anti-IL-7 Ab, suggesting that IL-7 produced by the adherent layer was required even in the earliest recognizable stages of human B cell lymphopoiesis. IL-1 alpha, IL-4, and TNF-alpha inhibited lymphoid progenitor colonies in a dose-dependent fashion. Neutralizing Ab to IL-1 alpha, IL-4, or TNF-alpha did not increase lymphoid progenitor colonies, suggesting that inhibitory concentrations of these cytokines are not constitutively elaborated in the adherent layer. Recombinant Steel factor and IL-6 as well as neutralizing Abs to these cytokines did not significantly affect lymphoid progenitor colonies, arguing against an important role for these cytokines in early human B lymphopoiesis. These results indicate that IL-7 provided by the bone marrow microenvironment is a critical growth factor at the earliest recognizable stages of human lymphopoiesis. IL-1 alpha, IL-4, and TNF-alpha have been shown to indirectly stimulate release of myeloid growth factors. The inhibition of lymphopoiesis by these cytokines suggests a possible mechanism for the observed reciprocal relationship between lymphoid and myeloid supportive bone marrow microenvironments.
Ryan
D H
DH
Department of Pathology, University of Rochester Medical Center, NY 14642.
Nuccie
B L
BL
Ritterman
I
I
Liesveld
J L
JL
Abboud
C N
CN
D000328:Adult; D001483:Base Sequence; D016207:Cytokines / Q000494:pharmacology*; D004253:DNA Nucleotidylexotransferase / Q000032:analysis; D006410:Hematopoiesis / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015851:Interleukin-7 / Q000096:biosynthesis / Q000494:pharmacology; D008214:Lymphocytes / Q000502:physiology*; D008969:Molecular Sequence Data; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D007375:Interleukin-1; D015851:Interleukin-7; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D004253:DNA Nucleotidylexotransferase