Analyses of H-2 restriction specificity of helper T cells in fully allogeneic bone marrow chimera in mice.

Using irradiation bone marrow chimeras to analyze restriction specificity of helper T cells, we found that recipient H-2 type dictated the H-2 type which the T cells recognize as self (adaptive differentiation). T cells from (H-2b----H-2k) chimeras cooperate with non-T cells bearing Iak to generate a vigorous PFC response to sheep erythrocytes (SRBC) in vitro, but not with genetically identical H-2b cells. However, when T cells from the chimeras and H-2b non-T cells were adoptively transferred into irradiated (donor X recipient) F1 mice with SRBC, marked responses were seen in recipient spleens where radio-resistant F1 macrophages might exist and act as antigen presenting cells (APC). From these in vitro and in vivo observations, we considered that in the primary antibody response to a T dependent antigen such as SRBC, only T cell-macrophage (APC) matching is required. In contrast, when T cells from H-2 incompatible chimeras which had been primed with SRBC in vivo were analyzed in vitro, these cells cooperated also with H-2b non-T cells. These findings indicate that there may be two separate stages of T cell differentiation during which the self restriction specificity is acquired: one appears to be responsive to intrathymic influences and is not associated with antigenic stimuli, and the other shows signs of being responsive to post-thymic stimuli and of involving antigenic presentation. Moreover, the latter appears to utilize the influence of donor type macrophages.