Allogeneic Leukocytes as a Possible Factor in Induction of AIDS in Homosexual Men

Gm, Shearer

doi:10.1056/nejm198301273080415

Cited by 64 publications

(2 citation statements)

References 7 publications

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“…A number of studies have emphasized the role of autoimmune mechanisms in the immunopathogenesis of AIDS. Disturbance of self–nonself recognition resulting from chronic activation of the immune system has been postulated to promote differential autoimmune deregulations, including GVHD condition ( 44 ), leukocyte alloimmunization ( 45 ), abnormal idiotype interactions ( 46 ), and increased cytokine secretion ( 47 ). Structural similarities between immunogenic HIV-1 envelope proteins and MHC and other key immunoregulatory molecules have recently been postulated ( 25 , 26 , 48 ) as the source of the chronic immune derangements, leading to the production of autoantibodies and clinical phenomena.…”

Section: Discussionmentioning

confidence: 99%

Cross-linking of Fas By Antibodies to a Peculiar Domain of gp120 V3 Loop Can Enhance T Cell Apoptosis in HIV-1–infected Patients

Silvestris

Nagata

Cafforio

et al. 1996

The Journal of Experimental Medicine

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Previous studies have demonstrated that T cell–reactive antibodies in HIV-1 infection contribute to lymphocyte depletion by cytotoxicity that involves differential membrane targets, such as the 43.5-kD receptor on CEM cells. Here, we show that these antibodies bind Fas as result of a molecular mimicry of the gp120. Both flow cytometry and immunoblotting using the human Fas-transfected mouse WC8 lymphoma revealed positive binding of immunoglobulin G from several patients to a 43.8-kD membrane receptor that also reacts with the CH11 anti-Fas monoclonal antibody. Specificity to Fas was further confirmed to chimeric recombinant human Fas-Fc by ELISA, whereas overlapping peptide mapping of a Fas domain (VEINCTR–N) shared by gp120 V3 loop demonstrated a predominant affinity to the full-length 10-mer peptide. Four anti-Fas affinity preparations greatly increased the subdiploid DNA peak of CEM cells similar to agonist ligands of Fas. In addition, anti-Fas immunoglobulin G strongly inhibited the [3H]thymidine uptake of CEM cells in proliferative assays, inducing a suppression as high as provoked by both CH11 mAb and recombinant human Fas ligand. Since anti-Fas were reactive to gp120, it is conceivable that antibodies binding that domain within the V3 region are effective cross-linkers of Fas and increase apoptosis in peripheral T cells. These results suggest that autologous stimulation of the Fas pathway, rather than of lymphocytotoxic antibodies, may aggravate lymphopenia in a number of HIV-1+ subjects.

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Section: Discussionmentioning

confidence: 99%

Cross-linking of Fas By Antibodies to a Peculiar Domain of gp120 V3 Loop Can Enhance T Cell Apoptosis in HIV-1–infected Patients

Silvestris

Nagata

Cafforio

et al. 1996

The Journal of Experimental Medicine

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“…The idea of infection transmitted by cells containing pathogens (“Trojan Horses”) predates the discovery of HIV as the agent of AIDS 64, 65 . Later, two independent groups found in vivo evidence that mouse spleen mononuclear cells are able to cross mouse vaginal epithelium after atraumatic inoculation in the vaginal lumen 66, 67 .…”

Section: Seminal Free and Cell-associated Virus In The Establishment mentioning

confidence: 99%

HIV‐1 Vaginal Transmission: Cell‐Free or Cell‐Associated Virus?

Barreto-de-Souza

Arakelyan

Margolis

et al. 2014

American J Rep Immunol

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The vast majority of new HIV infections in male-to-female transmission occurs through semen, where HIV-1 is present in two different forms: as free and as cell-associated virus. In the female lower genital tract, semen mixes with female genital secretions that contain various factors, some of which facilitate or inhibit HIV-1 transmission. Next, HIV-1 crosses the genital epithelia, reaches the regional lymph nodes, and disseminates through the female host. Cervico-vaginal mucosa contains multiple barriers, resulting in a low probability of vaginal transmission. However, in some cases HIV-1 is able to break these barriers. Although the exact mechanisms of how these barriers function remain unclear, their levels of efficiency against cell-free and cell-associated HIV-1 are different, and both cell-free and cell-associated virions seem to use different strategies to overcome these barriers. Understanding the basic mechanisms of HIV-1 vaginal transmission is required for the development of new antiviral strategies to contain HIV-1 epidemics.

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Lymphocyte alloantigenic challenge as a potential cofactor in HIV infection and progression to AIDS

Hoff¹,

Peterson²

1990

American J Hum Biol

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A hypothesis is developed that circulatory exposure to alloantigens found on lymphocytes triggers a series of events leading to suppression of the cell-mediated arm of the immune system and, therefore, that such alloantigenic challenge can be an important cofactor promoting infection with the human immunodeficiency virus (HIV) and development of the acquired immunodeficiency syndrome (AIDS) following infection. The explanatory model that is developed is based in large part on current knowledge of the results of fetal lymphocyte alloantigenic challenge of the maternal immune system. It is our contention that the maternal response which leads to suppression of cell-mediated immunity is a mechanism promoting survival of the fetal "allograft," and that this mechanism is an evolutionary adaptation in humans and other placental mammals. We also hypothesize that circulatory exposure to these same alloantigens leads to an immunosuppressive state which enhances survival of HIV in an exposed individual and augments the immunosuppressive action of HIV in promoting progression to clinical AIDS. Findings from studies of individuals who are at risk for exposure to lymphocyte alloantigenic challenge and from HIV infected patients are reviewed and discussed in light of this hypothesis.

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Allogeneic Leukocytes as a Possible Factor in Induction of AIDS in Homosexual Men

Cited by 64 publications

References 7 publications

Cross-linking of Fas By Antibodies to a Peculiar Domain of gp120 V3 Loop Can Enhance T Cell Apoptosis in HIV-1–infected Patients

Cross-linking of Fas By Antibodies to a Peculiar Domain of gp120 V3 Loop Can Enhance T Cell Apoptosis in HIV-1–infected Patients

HIV‐1 Vaginal Transmission: Cell‐Free or Cell‐Associated Virus?

Lymphocyte alloantigenic challenge as a potential cofactor in HIV infection and progression to AIDS

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