Unique patterns of surface receptors, cytokine secretion, and immune functions distinguish T cells in the bone marrow from those in the periphery: impact on allogeneic bone marrow transplantation

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Abstract
The “conventional” NK1.1− T cells from mouse blood and marrow were compared with regard to surface receptors, cytokine secretion, and function. Most blood NK1.1−CD4+ and CD8+ T cells expressed the naive CD44int/loCD62LhiCD45RBhiT-cell phenotype typical of those in the peripheral lymphoid tissues. In contrast, most marrow NK1.1−CD4+ and CD8+ T cells expressed an unusual CD44hiCD62LhiCD45RBhiphenotype. The blood NK1.1− CD4+ T cells had a naive T-helper cytokine profile and a potent capacity to induce lethal graft versus host (GVH) disease in a C57BL/6 donor to a BALB/c host bone marrow transplantation model. In contrast, the marrow NK1.1− CD4+ T cells had a Th0 cytokine profile and failed to induce lethal GVH disease, even at 20-fold higher numbers than those from the blood. NK1.1− CD8+ T cells from the blood but not the marrow induced lethal GVH disease. Nevertheless, the marrow NK1.1− CD8+ T cells induced potent antitumor activity that was augmented by marrow NK1.1− CD4+ T cells and facilitated hematopoietic progenitor engraftment. The inability of marrow CD4+ and CD8+ T cells to induce GVH disease was associated with their inability to expand in the blood and gut of allogeneic recipients. Because neither the purified marrow CD4+ or CD8+ T cells induced GVH disease, their unique features are desirable for inclusion in allogeneic bone marrow or hematopoietic progenitor transplants.