T-cell development
Bone marrow-derived hemopoietic precursors commit to the T cell lineage only after arrival in the thymic microenvironment. Heinzel, K. et al. J. Immunol. 178, 858–868 (2007)
Identification of a T lineage-committed progenitor in adult blood. Krueger, A. & von Boehmer, H. Immunity 26, 105–116 (2007)
The nature of the precursor cells that enter the thymus and become T cells and where commitment to the T-cell lineage occurs are controversial issues in T-cell biology. Two recent papers further add to this controversy, with one claiming that T-cell-lineage commitment occurs after entry to the thymus, and the second claiming that T-cell-committed precursors can be isolated from adult mouse blood.
Using single-cell analysis, Heinzel et al. show that the earliest precursor cells in the mouse thymus retain the capacity to develop into B cells, natural killer cells and dendritic cells as well as T cells. Only when these precursors are exposed to Notch signals intrathymically do they lose their potential to develop into non-T cells. Furthermore, T-cell precursors from the bone marrow are much less sensitive to Notch-mediated signals than thymic precursors, arguing against the idea that the bone marrow is the site of T-cell-lineage commitment.
By contrast, Krueger and von Boehmer, using transgenic reporter mice, in which human CD25 is expressed under the control of the pre-T-cell-receptor promoter, were able to isolate T-cell progenitors from adult mouse blood. These cells generated T cells when cultured in vitro using the OP9–DL1 culture system, and in vivo after transfer into mice deficient in T cells and interleukin-2 (IL-12). No B cells were detected after in vivo transfer, and only a few were detected after in vitro culture. Similar frequencies of precursors were isolated from thymus-deficient and wild-type mice, which indicates that the precursors are T-cell-lineage committed prethymically rather than intrathymically.
These two studies provide further information to fuel the ongoing controversy about the nature of T-cell lineage-committed T-cell precursors.
HIV
The diversity of the HIV-1 envelope proteins allows the virus to effectively evade antibody-mediated neutralization. Only two envelope glycoprotein 120 (gp120)-reactive antibodies (b12 and 2G12) with broad neutralizing reactivity against a range of primary HIV-1 isolates have been identified so far. In this study, Zhou and colleagues provide a molecular description of the interaction between b12 and gp120
The authors generated stabilized gp120 molecules that stayed in the CD4-bound confirmation even in the absence of CD4, and used these constructs to assess the CD4-binding site, which must be conserved in order to mediate virus binding and cellular entry. CD4 and b12 were found to bind to overlapping sites on a conformationally invariant surface of gp120, which is the initial contact site for CD4 prior to the gp120 rearrangements that are necessary to mediate viral entry.
Rights and permissions
About this article
Cite this article
In Brief. Nat Rev Immunol 7, 173 (2007). https://doi.org/10.1038/nri2048
Issue Date:
DOI: https://doi.org/10.1038/nri2048