Regulation by the H-2 gene complex of delayed type hypersensitivity

Vadas, Mathew A.; Miller, J. F. A. P.; Whitelaw, Alison; Gamble, Jennifer R.

doi:10.1007/bf01575653

Cited by 89 publications

(48 citation statements)

References 21 publications

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“…The lesion may indeed result from the inability of UV-treated APCs to provide the required stimulus to the T lymphocyte with which it interacts specifically. It is further possible that this ineffective antigen presentation, occurring as a consequence of UV irradiation-induced functional changes, stimulates the generation of suppressor T cells rather than Lyt 1+ effector cells (12).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the APC has been proposed as the site of expression of immune response (Ir) genes in some antigenic systems (8)(9)(10). Other studies have revealed that H-2 genetic identity between the antigen-coupled APC and the recipient is required for maximal induction (11,12) and transfer of T cell-dependent delayed type hypersensitivity (DTH) responses. Moreover, similar genetic identity at the I region of H-2 between APC and T helper cells is required for maximal priming effects (13)(14)(15).…”

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confidence: 99%

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Impairment of antigen-presenting cell function by ultraviolet radiation.

Greene

Kripke

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

231

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UV light irradiation of BALB/c mice was found to result in impairment of antigen-presenting cell function. Adherent trinitrophenyl-derivatized cells from the peritoneal exudate cell population or the spleen of UV-treated donors could not induce hapten-specific delayed hypersensitivity responses in UV-irradiated syngeneic mice, whereas adherent trinitrophenyl-derivatized cel1s from normal mice were able to do so. The failure to induce immunity in UV-treated mice by utilizing UV-treated adherent antigen-presenting cells was associated with the development of antigen-specific supgressor T cells. The implication of these results for UV-inducescarcinogenesis is discussed.UV light irradiation plays an immunologic role in the induction of certain murine fibrosarcomas and squamous carcinomas (1-3) in addition to its carcinogenic action. UV-irradiated mice are unable to reject UV-induced tumors that are highly antigenic and that are rejected by normal syngeneic recipients. Recent work suggests that the lack of tumor rejection is due to the presence of suppressor T lymphocytes (TJ) in the lymphoid organs of UV-irradiated mice (4-6). The origin of T, and their relationship to UV irradiation is incompletely understood. However, a recent suggestion that processing of antigen is deficient early in the course of UV irradiation (4) raised the possibility that T, induction might result from a defect in the afferent limb of the immune response. To resolve this issue, we have evaluated the effects of UV irradiation on cellular immunity to hapten conjugates of syngeneic cells and have investigated the mechanism of this process.There is substantial evidence that antigen-presenting cells (APCs) participate critically in the generation of immune responses (7). Indeed, the APC has been proposed as the site of expression of immune response (Ir) genes in some antigenic systems (8)(9)(10). Other studies have revealed that H-2 genetic identity between the antigen-coupled APC and the recipient is required for maximal induction (11, 12) and transfer of T cell-dependent delayed type hypersensitivity (DTH) responses. Moreover, similar genetic identity at the I region of H-2 between APC and T helper cells is required for maximal priming effects (13)(14)(15).Previous work has shown that UV irradiation of guinea pig skin rendered it unreactive to topical immunizing doses of dinitrochlorobenzene (16). Moreover, UV irradiation of a skin test site in a human subject markedly decreased the development of the local DTH reaction (17). Furthermore, recent studies in which lymphoid cells were exposed to UV irradiation in vitro (18)(19)(20) demonstrated that UV treatment rendered them incapable of serving as allogeneic stimulators in a mixed leukocyte reaction despite the fact that the H-2 encoded antigens on such cells were not discernibly affected or diminished. Still more recently, human lymphoid cells exposed to UV irradiation in vitro were reported not to efficiently stimulate or present hapten to antigen-reactive cells in an in vitro prolif...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Impairment of antigen-presenting cell function by ultraviolet radiation.

Greene

Kripke

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

231

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“…Vadas et al (20) have recently shown that contact sensitivity to DNFB can be successfully transferred between donor and recipient mouse strains which share only the H-2K and/or H-2D regions of the MHC. It should be pointed out that this association does not hold in all DTH systems, since I region compatibility is required for transfer of DTH to fowl gamma globulin (6,20). In terms of tolerance to DNFB contact sensitivity, Phanuphak et al have shown that tolerization with DNBSO3 leads to the induction of hapten-specific Ts (21) which block the afferent limb of sensitization by inhibiting antigeninduced DNA synthesis (14).…”

Section: Discussionmentioning

confidence: 99%

Genetic restrictions for the induction of suppressor T cells by hapten-modified lymphoid cells in tolerance to 1-fluoro-2,4-dinitrobenzene contact sensitivity. Role of the H-2D region of the major histocompatibility complex.

Miller

Claman

1978

The Journal of Experimental Medicine

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Gene products of the major histocompatibility complex (MHC) 1 are associated with various effector and cooperative functions of immunocompetent lymphoid cells (1). The I region of the MHC is associated with the induction of helper T cells (2), the proliferative response of T cells to allogeneic cells (3) and to antigen-pulsed macrophages (4), cooperation of T helper cells with B cells (5), and the adoptive transfer of delayed-type hypersensitivity (DTH) to fowl gamma globulin (6). Gene products of the H-2K and/or H-2D regions of the MHC are associated with T-cell-mediated cytolysis of virus-infected (7) or hapten-modified (8) target cells, and the~transfer of DTH to murine lymphocytic choriomeningitis virus (9).We have recently been studying the induction and mechanisms of haptenspecific T-cell tolerance to 1-fluoro-2,4-dinitrobenzene (DNFB) contact sensitivity by using dinitrophenyl (DNP)-modified lymphoid cells (DNP-LC) as tolerogens (10). Tolerance induced by DNP-LC has been functionally separated into two mechanisms-clone inhibition and the participation of suppressor T cells (Ts) (11). We have also reported that the induction of Ts by DNP-syngeneic LC (syninduced Ts) (12) as well as the expression of Ts induced by DNP-allogeneic LC (alloinduced Ts) (13) is genetically restricted by MHC gene products. In the present report, we have investigated these genetic restrictions by using congenic resistant mouse strains. The results indicate that both syninduced and aUoinduced Ts are activated by hapten-modified determinants coded for by the H-2D region of the MHC. Furthermore, the results show that alloinduced Ts are

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“…Thus, the I-A, I-B, and I-E or I-C subregions contain genes regulating specific immune responses (Ir genes) (3,4), whereas the I-A or I-B and I-C or S regions control specific immune suppression (Is genes) (5). The I-A, I-J, and I-E-I-C subregions also contain genes controlling mixed lymphocyte and graft-vs-host reactions (2); the I-A subregion has been shown to also code for cell-surface components responsible for determining efficient T cell-B cell (6) or T cell-macrophage (7,8) interactions. Recently, genetic evidence has accumulated indicating that the I-A subregion codes for T cell-derived specific helper factors (9) whereas the I-J subregion codes for both T cell-derived suppressor factors and surface alloantigens on T suppressor cells (10)(11)(12).…”

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confidence: 99%