The currently accepted view is that autoreactive cells in OS and transplacental-acquired maternal T cells cannot occur concomitantly in the same patient. This point was emphasized in a recent report defining the absence of maternal engraftment as one of the OS criteria . Indeed, none of 39 OS cases in which transplacental-acquired maternal T cells were investigated was positive for maternal chimerism . Overall, transplacental-acquired maternal T cells have been reported in 40% of SCID patients, but in none when OS was diagnosed. Moreover, 62% of B-SCID patients (e.g. RAG deficiency) who were free of signs suggestive of OS were found to have signs of maternal T cell engraftment [i.e. typical graft-versus-host disease (GVHD) symptoms] . In some rare cases, these cells either conferred immunity and protection against infection  or they caused allograft rejection and immune cytopenias . A massive expansion of maternal T cells in response to Epstein–Barr virus infection in a patient with X-linked SCID has been also reported . The first report of long-term co-existence of autologous T cells and high levels of engraftment of haploidentical maternal T cells was published recently . In that study by Cattaneo et al., analysis of the autologous cells revealed a naive phenotype with a polyclonal repertoire of proliferating and activated cells in vivo. The residual function and the diversified repertoire of the autologous cells contributed to the excellent clinical status of the reported patient, who had no obvious signs suggestive of OS . It is possible that the co-existence of autologous and maternal cells in patients exhibiting milder OS symptoms was simply not detected, rather than that these cells are mutually exclusive. Here, we show the co-existence of autologous and maternal oligoclonal expanded T cells in a case of an SCID patient with a milder form of OS. Our patient presented with typical clinical features and was found to have a homozygous four nucleotides deletion in RAG1, resulting in frameshift and premature stop codon. We speculate that the frameshift deletion alleles remain partially functional for recombination, thus explaining his partial rearrangement phenotype, as was shown previously for OS patients with a similar type of mutation . Indeed, our patient displayed milder OS clinical and laboratory characteristics (e.g. mild skin rash, eosinophilia and alopecia and a low IgE level) and he responded very rapidly to low doses of steroids. In contrast to Cattaneo et al.'s  findings, our patient's autologous cells had a clonal representation, which probably contributed to the severity of his immunodeficiency. We confirmed our patient's oligoclonality by using different methods for investigating both the TCR-Vβ and TCR-γ rearrangements. Interestingly, his symptoms were less severe than would be expected from the nature of the autoreactive cells, suggesting the presence of a protective mechanism. His symptoms were, however, more severe than those seen in the GVHD that is related to the presence of maternal cells in SCID patients . Indeed, both cell populations were visualized in his peripheral blood. Moreover, fluorescence activated cell sorter (FACS) analysis demonstrated that both cell populations were clonal. Also, interestingly, is the finding that the maternal cells had better representation of the TCR-Vβ families and a greater number of cells expressing CD4+CD25+FoxP3+, supporting our hypothesis that these cells provide some degree of immunity and prevent autoimmunity. We have shown previously that SCID patients with 100% maternal cells had greater amounts of CD4+CD25+FoxP3+ than SCID patients with barely detectable maternal cells. These cells were not secreting interferon-gamma or interleukin-2, suggesting that they were functional Tregs . We therefore think that co-engraftment of maternal cells could end up being associated with a distinctly milder OS phenotype, which could be more prevalent if it were sought. Further functional studies and the reporting of more similar patients are needed to confirm our hypothesis that transplacental-acquired maternal T cells have such a tolerance capacity.
In summary, we describe the co-existence of significantly high amounts of both autologous and maternal cells in an SCID patient. While the oligoclonal pattern of the TCRs in both cell populations appears to contribute to the severity of the immunodeficiency observed in our patient, the presence of maternal cells may have lessened the autoimmune manifestations associated with OS.