HY Immune Tolerance Is Common in Women without Male OffspringReportar como inadecuado




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Background

Sex difference is an established risk factor for hematopoietic stem cell transplantation HSCT-related complications like graft versus host disease GVHD. CD8pos cytotoxic T cells specific for Y chromosome-encoded minor Histocompatibility antigens HY play an important role therein. Prior to HSC donation, female donors may encounter HY antigens through fetomaternal or transmaternal cell flow, potentially leading to the induction of HY-specific cytotoxic or regulatory immune responses. Whether HY priming occurs independent of parity, and whether HY priming is dependent on the presence of male microchimerism, is as yet unknown.

Methods

We investigated the presence of HY-specific regulatory T cells Treg and male microchimerism in 45 healthy women with a fully documented pregnancy and family history. HY peptide-induced linked suppression, a commonly reported functional feature of CD4pos and CD8pos Treg, was measured by trans vivo Delayed Type Hypersensitivity testing. As source of HY antigens, male microchimerism was analyzed by real-time PCR and defined by the presence of male DNA in at least one purified leukocyte cell type.

Results

HLA class I or class II restricted HY-specific Treg were detected in 26-42 62% women eligible for analysis. The prevalence of HY-specific Treg was significantly higher in women who had never given birth to sons than in women with male offspring p = 0.004. Male microchimerism could be detected in 24 out of 45 53% women but did not correlate with the presence of HY specific Treg.

Conclusions

HY-specific Treg in women with male offspring have been described previously. Here we show for the first time that, in fact, HY specific Treg are more common in nulliparous women and in parous women with female offspring. Their presence is independent of the presence of male microchimerism. Whether HY-specific Treg presence in female stem cell grafts might decrease the GVHD incidence in male HSCT recipients needs to be investigated.



Autor: Miranda P. Dierselhuis, Ewa Jankowska-Gan, Els Blokland, Jos Pool, William J. Burlingham, Astrid G. S. van Halteren , Els Goulmy

Fuente: http://plos.srce.hr/



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