Synergy During in Vitro Cytotoxic Allograft Responses

T-T-cell interactions involved in delayed hypersensitivity (DH) response have been studied by employing delayed foot pad assay to methylated human serum albumin in C57BL/6J mice. The DH response, one of the T-cell manifestations of cell-mediated immune response is suppressively regulated by T cells and such observation was based on studies of age-associated kinetics of foot pad reaction and effects of cell transfer and adult thymectomy on developing DH response. These suppressively regulatory T cells in DH have a life span of less than 4 wk and a constant derivation from the thymus is required. Such cells are numerous in the young mouse thymus and few in the spleen and thymus of old mice. On the one hand, the presence of a long-lived effector T-cell population was suggested in DH. These cells are numerous in the spleen and are low responders to phytohemagglutinin in vitro. It is assumed that these suppressive T cells interact with antigen-reactive cells at their proliferating stage by recognition of the iodiotypic difference through surface receptors. As in the case of graft-vs.-host and humoral response in vivo, three different subsets of immune competent cells participate in the DH response. These cells consist of one specifically antigen-reactive T cell, one suppressive regulatory T cell, and one bone marrow-derived cell, a macrophage that responds to a chemical mediator from sensitized effector T cells and that develops a DH skin lesion nonspecifically.

Section: Effect Of Aging Adult Thymectomy and Additionally Transfermentioning

confidence: 93%

“…sion in vitro have been observed in mixed lymphocyte reactions (MLR) (8)(9)(10)(11) and in cytotoxic allograft responses (12)(13)(14)(15). Delayed hypersensitivity (DH) is an important phenomenon manifested by T-cell activity, yet few papers have discussed such activity.…”

Section: Gershon Et Al (5 6) and By Hardin Et Al (7) T-t-cell Coomentioning

confidence: 99%

Studies on delayed hypersensitivity in mice. III. Evidence for suppressive regulatory T1-cell population in delayed hypersensitivity.

Morikawa¹,

Baba²,

Harada³

et al. 1977

“…Recent data from several laboratories (22,23) have shown that synergy results from interactions among thymocytes and peripheral T cells in cellular immunity to transplantation antigens. Our observations are consistent with this emerging concept of T-cell-T-cell interaction in cellular immune responses in the sense that they demonstrate that T lymphocytes may also exert a regulatory influence and suppress CL responses.…”

Section: Characterization Of Conmentioning

confidence: 99%

Cell-Mediated Immune Responses in Vitro

Peavy

Pierce

1974

114

The effects of soluble concanavalin A (Con A) or Con A-activated spleen cells on the generation of cytotoxic lymphocytes (CL) in mixed leukocyte cultures (MLC) were examined. Mitogenic concentrations of soluble Con A or small numbers of Con A-activated spleen cells substantially inhibited CL responses. The suppression was partial rather than absolute and was critically dependent upon the concentration and time of addition of soluble Con A or Con A-activated spleen cells to the MLC. Suppressive effects of Con-A activated spleen cells were mediated by T cells since suppressor cell activity was abrogated by treatment of spleen cells with anti-θ serum and complement before or after Con A activation. X irradiation of spleen cells before Con A treatment also abrogated generation of suppressor cell activity. After activation by Con A, however, the function of suppressor cells was radioresistant. Although the precise mechanism(s) of suppression is, as yet, unknown, the precursors of CL must be exposed to Con A-activated cells during the early phases of the immune response for suppression to occur. Kinetic studies revealed that suppression of CL responses was not due to a failure to initiate an immune response, but represented a response which developed initially, but subsequently aborted. The relevance of these observations to the concepts of T-cell-T-cell interaction and regulatory control of immune responses by T cells is discussed.

“…Originally, T-T collaboration was thought of in terms of synergy between thymocytes and lymph node cells but the functional contributions of each were not characterized (1,2) . The participation of two collaborating cell types in the induction of a cytotoxic response was also shown by later work demonstrating that the cytotoxic T precursor had Ly2,3 antigens on its surface and was apparently specific for H-2K and D region encoded determinants although the helper/amplifier cell had Lyl antigen and appeared to be specific for determinants encoded in the I region of the H-2 gene complex (3) .…”

mentioning

confidence: 99%

In vitro generation of antigen-specific helper T cells that collaborate with cytotoxic T-cell precursors.

Baum¹,

Pilarski²

1978

Antigen-specific helper T cells are required in the generation of cytotoxic T cells from thymocyte precursors. We have demonstrated that these alloantigen-specific helper cells can be generated in vitro and that both the quantity and quality of the helpers appear to be superior to the help obtained from unprimed spleen cells. Optimal helper cell activity is produced at day two of culture when CBA splenic helper precursors are stimulated by irradiated allogeneic spleen cells. Helper cell precursors are antigen-specific cells which cannot be instructed to express forbidden receptor specificities and bear theta antigen on their surface. The helper effectors are radioresistant, theta-bearing, and antigen-specific cells.