Detection and characterization of functional T cells in mice with severe combined immune deficiency

Abstract

CD3+ alloresponsive T cell clones were derived from mice with severe combined immune deficiency (scid mice). T cell receptor beta and gamma gene rearrangements were analyzed to obtain insight into the nature and origin of these clones. We hypothesized that developing scid lymphocytes with an active, impaired recombinase system might generate functional lymphocytes by rare productive rearrangements at two critical antigen receptor loci. One alloresponsive clone showed evidence of both normally rearranged T cell receptor genes and genes with abnormal J region-associated deletions, supporting this hypothesis. Four additional alloresponsive clones, however, showed only conventional gene rearrangements. These data leave open the possibility that the recombinase activity, believed defective in scid mice, may be normalized in rare early B and T lymphoid cells or their precursors, to give rise to functional lymphocytes.