The proliferative response of immune human T lymphocytes to low concentrations of purified protein derivative (PPD) in vitro was found to require the presence of macrophages. By coculturing different combinations of immune T lymphocytes and allogeneic macrophages with PPD in low concentration, optimal stimulation (that is, as efficient as the autologous combinations) was shown to require HLA-D identity between the macrophages and responding T cells. Identity for HLA-A and -B appeared to be of less or no importance. It is concluded that membrane structures encoded by HLA-D or closely linked loci are involved in the human macrophage/T-lymphocyte interaction in the proliferative response to PPD, much in the same way as the Ia antigens of rodents.

The response of T cells from sensitized individuals to low doses of PPD in vitro is macrophage-dependent. By testing different allogeneic combinations of macrophages and T lymphocytes, it was found that an optimal response required that antigen be presented by macrophages sharing at least one of the HLA-D determinants of the T cell donor. Antisera recognizing HLA-A, -B or -DR antigens were found to be able to inhibit this proliferative response. The anti-HLA-DR antisera were found to exert their inhibitory effect only when directed towards an antigen shared by the donors of the T lymphocytes and the macrophages. Anti-HLA-A and -B sera, however, had an inhibitory effect when reactive with the responding T lymphocytes, irrespective of their reactivity with the cooperating macrophages. It is concluded that an optimal secondary response of in-vivo-immunized T lymphocytes to PPD requires the combined recognition of the antigen and 'self' membrane structures encoded by the HLA-D locus.

Optimal proliferative response of T lymphocytes to purified protein derivative of tuberculin (PPD) in vitro requires that antigen be presented by autologous macrophages or allogeneic macrophages sharing HLA-D/DR determinants with the T cell donor. In some cases, however, T cells may respond to a limited extent to PPD in association with macrophages expressing different HLA-D/DR determinants. In this paper experiments are presented where various combinations of T cells and HLA-D/DR disparate macrophages were stimulated with PPD. We often found a stronger PPD-specific response in HLA-D/DR-incompatible combinations in which the macrophages carried HLA-DR antigens known from serological studies to be cross-reactive with those of the T cell donor than in combinations in which this was not the case. Thus, the cross-reactions detected by serology may sometimes be reflected on a functional level in T lymphocyte/macrophage cooperation.

The proliferative response of sensitized human T cells to low concentrations of purified protein derivative of tuberculin (PPD) in vitro has previously been shown to depend on the presence of autologous or HLA-D-compatible macrophages (M phi). In this paper we present evidence that the M phi/T cell interaction requires viable M phi and does not involve a soluble factor. T cells from neonates do not respond to PPD in our system, while M phi from neonates are able to present PPD to T cells from HLA-D matched sensitized adults. It is also demonstrated that the previously reported HLA-D restriction of T cell/M phi cooperation is not due to T cell mediated killing of allogeneic macrophages in vitro.

The proliferative response of sensitized human T lymphocytes to purified protein derivative (PPD) and to trinitrophenyl (TNP)-conjugated autologous cells in vitro is restricted by self HLA-D/DR determinants. Here we report that the PPD-specific response is strictly related to the content of phagocytosing cells (macrophages, Mphi) in the cultures and that an optimal PPD response occurred at a T/Mphi ratio between 10:1 and 5:1. B-cell-enriched suspensions, which also express the HLA-D/DR determinants, were not able to replace the macrophages in this HLA-D/DR-restricted response. On the other hand, TNP-treated similarly prepared B cells were in most instances effective in inducing a secondary TNP-specific response of in vitro-sensitized T cells.