Functional T cell deficits after bone marrow transplantation across minor histocompatibility barriers: effects of graft-vs-host disease on precursor frequency of reactive cells.

We have studied T cell responses in mice transplanted with bone marrow from H-2-identical, minor histocompatibility loci-nonidentical donors (B10.BR----CBA) in which graft-vs-host disease is induced by the addition of donor T cells. T cell responses to mitogen were examined both in high density, conventional bulk cultures and by limiting dilution analysis. Long-lasting deficits in the frequency of functional T cells were observed, for both IL 2-producing and cytotoxic cells, in proportion to the severity of the graft-vs-host disease induced. These deficits did not reflect a corresponding loss of Thy-1+ cells nor a loss of function in conventional cultures in mice studied at later times after bone marrow transplantation. These deficits in reactive cells are not completely correctable with IL 2, and provide further insight into the nature of T cell reconstitution of the immune system after bone marrow transplantation.