To characterize the cytokine production profile of male‐offspring T cells reactive against maternal major histocompatibility complex (MHC) antigens present in the peripheral blood and/or skin from women with systemic sclerosis (SSc).

T cell clones were generated from peripheral blood and/or skin biopsy specimens from 3 women with SSc of recent onset and from peripheral blood from 3 healthy women, all of whom had 1 male child. All clones were screened for their proliferative response in vitro to maternal MHC antigens by measuring ³H‐thymidine uptake and for their expression of Y chromosome by using fluorescence in situ hybridization. The concentrations of interferon‐γ and interleukin‐4 (IL‐4) released by T cell clones in response to maternal MHC antigens were evaluated in culture supernatants, using appropriate enzyme‐linked immunosorbent assays.

Thirty‐nine of 202 T cell clones generated from women with SSc and 11 of 312 from healthy women proliferated in vitro in response to maternal MHC antigens. Seven MHC‐reactive T cell clones obtained from women with SSc and 1 obtained from healthy women exhibited the Y chromosome, thus indicating that the clones were derived from T cells of male offspring. All clones generated from male‐offspring T cells of SSc women (but not from those of healthy women) produced significantly higher levels of IL‐4 in response to stimulation with maternal MHC antigens than did all other clones generated from the same women. The other clones proliferated in response to maternal or allogeneic MHC antigens but did not exhibit the Y chromosome.

Male‐offspring T cells that are present in the blood and skin of women with SSc and react with maternal MHC antigens exhibit a Th2‐oriented profile, supporting the possibility that a chronic graft‐versus‐host reaction attributable to long‐term microchimerism plays a pathogenic role in SSc.