Immunological and functional differences between cord and peripheral blood.

It is generally agreed that cord blood (CB) transplantation represents an encouraging alternative to bone marrow (BM) transplantation. There are a variety of reasons for this, the two most controversial being (1) whether there is less graft-versus-host disease (GVHD) with CB compared to BM transplantation; and (2) whether we can use more HLA mismatches with CB transplantation? If these are true then CB may generate a lower 'immunological response' compared to transplantation with adult cells. Why this may be is unknown, however recently there has been much work which compared the immunological function of CB and adult monocytes. This work may begin to explain some of the differences we see with different transplants. The most common explanation for reduced CB cell function is that it is naive since, compared to adult mononuclear cell populations, there are (a) higher levels of CD4+ CD45RA+ cells; (b) lower antigen and mitogen specific T cell proliferation; (c) lower cytokine production on stimulation; and (d) a more polyclonal T cell receptor repertoire compared to adult blood. However, lymphocyte naiveté may not be the only answer since it is possible these naive phenomena, noted in vitro are bypassed in vivo. We have evidence that there are differences in the soluble factors secreted into the serum which altered the function of cord and adult lymphocytes. We have analysed the effect of heat-inactivated sera on the function of T cell proliferation by looking at the mitogen and cytokine-specific proliferative responses. Using adult peripheral blood mononuclear cells we show that adult sera will enhance the proliferative responses whereas CB sera has no effect. These results suggest that there is a factor within mature serum which is absent in foetal serum. This factor is, in part, responsible for the proliferation of T cells and its absence could explain the reduced proliferative responses of CB compared to adult T cells. Furthermore, it may shed some light on preliminary observations that CB transplantation gives rise to a low incidence of GVHD.