Virgin and memory T cells reciprocally express high levels of the RA or the RO isoforms of CD45, respectively. In an examination of T cell expression of these two CD45 isoforms during human development, the RO+RA- "memory" T cells were infrequent in the newborn blood and spleen, but comprised approximately half of the T cells in adult tissues. These anticipated findings probably reflect the immunologic naivete of the newborn. Surprisingly, however, RO+RA- T cells were relatively abundant in fetal spleen and in cord blood samples from premature births, comprising approximately 25% and 10% of the T cells in these tissues, respectively. This early peripheral wave of RO+RA- T cells was composed of polyclonal T cells in both the CD4 and CD8 subpopulations. The fetal RO+ cells of CD4+ phenotype frequently expressed the CD25-alpha chain subunits that characterize high affinity IL-2 receptors, and were able to proliferate in response to exogenous IL-2. In further contrast with their RO+ memory T cell counterparts in adults, the fetal T cells were unresponsive to mitogenic anti-CD2 and anti-CD3 antibodies. We conclude that the data suggest an embryonic population of autoreactive T cell clones with anergic characteristics.

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