Figure 1
Figure 1. Reconstitution of the T-cell compartment after UCBT. Conditioning chemoradiation prior to UCBT results in profound lymphopenia and immunodeficiency of the host. T-cell reconstitution after UCBT is achieved by 2 independent mechanisms: the thymus-independent pathway of T-cell reconstitution predominates in the early posttransplant period and is mediated by adoptively transferred UCB T cells, which are uniformly naive and do not transfer protective immune memory, or recipient T cells that survive conditioning. These T-cell populations undergo peripheral expansion in response to lymphopenia and high cytokine levels (IL-7, IL-15, etc), or oligoclonal proliferation upon interaction with cognate antigen. Overtime, this early peripheral T-cell expansion results in late effector memory T-cell skewing and contraction of the T-cell repertoire diversity, and is associated with impaired immunologic responses to antigens. Reconstitution of a functionally competent T-cell compartment with broad antigenic specificity eventually requires the de novo production of naive T cells by the thymus of the UCBT recipient. This thymus-dependent pathway of T-cell reconstitution is a prolonged multistep process. LMPs contained in the UCB graft or arising from the engrafted donor-derived HSCs migrate via circulation and repopulate the thymus with thymocyte precursors that can reconstitute thymopoiesis. The thymus provides the essential microenvironment (stroma) that supports T-cell proliferation, selection, and differentiation into RTEs. Several factors can delay the recovery of thymopoiesis after UCBT, including low number of LMPs (as a result of low nucleated cell dose of UCB and delayed engraftment), advanced recipient age with resultant thymic involution and thymic damage from the conditioning chemoradiation or GVHD. Although slow, the thymus-dependent mechanism is imperative for the renewal of peripheral T-cell pool and constant export of new naive T cells with broad TCR repertoire diversity, capable of responding to a great spectrum of antigens.

Reconstitution of the T-cell compartment after UCBT. Conditioning chemoradiation prior to UCBT results in profound lymphopenia and immunodeficiency of the host. T-cell reconstitution after UCBT is achieved by 2 independent mechanisms: the thymus-independent pathway of T-cell reconstitution predominates in the early posttransplant period and is mediated by adoptively transferred UCB T cells, which are uniformly naive and do not transfer protective immune memory, or recipient T cells that survive conditioning. These T-cell populations undergo peripheral expansion in response to lymphopenia and high cytokine levels (IL-7, IL-15, etc), or oligoclonal proliferation upon interaction with cognate antigen. Overtime, this early peripheral T-cell expansion results in late effector memory T-cell skewing and contraction of the T-cell repertoire diversity, and is associated with impaired immunologic responses to antigens. Reconstitution of a functionally competent T-cell compartment with broad antigenic specificity eventually requires the de novo production of naive T cells by the thymus of the UCBT recipient. This thymus-dependent pathway of T-cell reconstitution is a prolonged multistep process. LMPs contained in the UCB graft or arising from the engrafted donor-derived HSCs migrate via circulation and repopulate the thymus with thymocyte precursors that can reconstitute thymopoiesis. The thymus provides the essential microenvironment (stroma) that supports T-cell proliferation, selection, and differentiation into RTEs. Several factors can delay the recovery of thymopoiesis after UCBT, including low number of LMPs (as a result of low nucleated cell dose of UCB and delayed engraftment), advanced recipient age with resultant thymic involution and thymic damage from the conditioning chemoradiation or GVHD. Although slow, the thymus-dependent mechanism is imperative for the renewal of peripheral T-cell pool and constant export of new naive T cells with broad TCR repertoire diversity, capable of responding to a great spectrum of antigens.

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