T cell vaccination benefits relapsing progressive multiple sclerosis patients: a randomized, double-blind clinical trial.

Background: T-cell vaccination (TCV) for multiple sclerosis (MS) refers to treatment with autologous anti-myelin T-cells, attenuated by irradiation. Previously published clinical trials have been all open-labeled.

Aim: To evaluate the safety and efficacy of TCV in progressive MS, in a double-blind, controlled clinical trial.

Peptide therapy for anti-CD4 autoimmunity in HIV-1 infection: toward the development of an autoimmune animal model.

Aiming to develop an animal model for anti-CD4 autoimmunity reflective of that observed in HIV-1 patients, we injected the selected peptides p1, p28 and p29 as the major immunogenic epitopes into HLA-DR4 and human CD4 transgenic DBA/16J mice, as well as into C57BL/6 and DBA mice. We document a decrease of CD4+ cells in peripheral blood and spleen after immunization with the human CD4-p28 immunogenic peptide of transgenic mice expressing human CD4, human HLA class II and mouse class II I-A(q) (HLA-DR4-huCD4-I-A(q+)); however, no decrease of CD4 cells was found in transgenic HLA-DR4-huCD4-I-A(q-) mice or in control C57BL/6 and DBA immunized mice. Overall, the consistency of CD4 reduction and immunological recognition of p28 peptide favors the HLA-DR4-huCD4-I-A(q+) mouse as the most promising autoimmune mouse model.

Autologous T-cell vaccination for multiple sclerosis: a perspective on progress.

T-cell vaccination (TCV) is a unique approach to induce immune regulation that may have importance in the treatment of autoimmune diseases, including multiple sclerosis (MS). TCV employs a classic vaccine strategy of injecting an attenuated form of the disease-causing agent--in this case, myelin-reactive T cells--that have been selected and expanded from each MS donor and then re-injected after irradiation to induce protective immunity. This anti-T-cell immunity consistently results in selective deletion or regulation of the targeted pathogenic T cells in vivo.

Major CD4 epitopes involved in anti-CD4 T-cell autoimmunity in HIV-1 patients.

We studied HIV-positive and -negative subjects for T-cell reactivity to rCD4, and found that 80% of 25 tested HIV-infected patients and 25% of controls manifested T-cell proliferation responses to rCD4. We mapped the major CD4 immunogenic epitopes among the CD4+ responders of both groups by testing T-cell proliferation responses to 31 synthetic overlapping peptides from the human CD4 molecule. Such responses to p1, p4, p14, p21, p28 and p29 were significantly higher in the eight infected patients and, with the exception of p14, these peptides differed from those found in three HIV-negative controls (p11, p14 and p27).

Therapeutic AIDS vaccines.

Therapeutic HIV vaccines represent promising strategy as an adjunct or alternative to current antiretroviral treatment options for HIV. Unlike prophylactic AIDS vaccines designed to prevent HIV infection, therapeutic vaccines are given to already infected individuals to help fight the disease by modulating their immune response. The first immunotherapeutic trial in AIDS patients was conducted in 1983.

Autoimmunity, alloimmunization and immunotherapy of AIDS.

The nature of clinical and physiological manifestations associated with HIV infection suggests that AIDS is an autoimmune disease. The conventional immunotherapeutic approaches aimed at enhancing the immune response against HIV have repeatedly failed when applied in the clinical practice. The results of several dozen therapeutic AIDS vaccine trials have consistently shown that while in vitro measured HIV-specific immune responses were evident as a result of vaccination the clinical improvement has been seldom observed.

Clinical experience with therapeutic AIDS vaccines.

Recently, there has been a renewed interest in therapeutic vaccination as an adjunct or alternative to current treatment options for HIV. The first immunotherapeutic trial relevant to this topic was published in 1983. Since then, several dozen therapeutic vaccine trials have been carried out.

T-cell vaccination against anti-CD4 autoimmunity in HIV-1 subtypes B and C-infected patients--an extended open trial.

This study is an extended clinical trial of the one initiated and reported in the Journal of Clinical Virology 2004;31S:S48-54. Thirteen HIV-1 patients (eight subtype B and five subtype C) that manifested T-cell autoimmunity to recombinant human CD4 (rCD4) were treated with T-cell vaccine composed of glutaraldehyde-treated autologous anti-CD4 reactive T-cells and compared to historical seven non-vaccinated HIV-1-infected subjects. This study proved to be feasible and safe.

T-cell vaccination against anti-CD4 autoimmunity in HIV-1 infected patients.

Background: Highly active antiretroviral therapy (HAART) is frequently associated with only partial restoration of CD4 T-cell levels. Autoimmunity to CD4 T-cells may account for the persistence of the CD4 T-cell lymphopenia in such cases.

Objective: To document T-cell autoimmunity to CD4 in HIV-infected patients and to determine if T-cell vaccination against CD4 autoimmunity is feasible and safe.

Characterization of new monoclonal antibodies that discriminate between soluble and membrane CD4 and compete with human anti-CD4 autoimmune sera.

In this report we present results on immunization of hu-CD4 C57Black/6J transgenic mice with HIV-1 gp120(451) complexed with its receptor protein, CD4. In addition to development of anti-gp120 antibodies, these mice also produced two anti-CD4 monoclonal antibodies, designated T6 and T9. Both these antibodies recognize soluble CD4 but not membrane associated CD4.

T cells and autoantibodies to human HSP70 in type 1 diabetes in children.

We studied T-cell proliferative responses (stimulation index: SI) and autoantibodies to human HSP60, HSP70 and HSP90 proteins in 25 children (mean age 10.1+/-3.8 years) newly diagnosed with Type 1 diabetes.

T cell proliferative responses of type 1 diabetes patients and healthy individuals to human hsp60 and its peptides.

T cell responses to peptide epitopes of the 60 kDa heat shock protein (hsp60) have been shown to play a role in the pathogenesis of type 1 insulin-dependent diabetes mellitus (IDDM) in mice. To test whether hsp60 autoimmunity might be involved in human type 1 diabetes, we studied T cell proliferative responses (stimulation index; SI) to intact human hsp60, to hsp60 peptides and to a recall antigen (tetanus toxoid) in 25 newly diagnosed type 1 diabetes patients, in 22 type 2 (non-insulin-dependent diabetes mellitus, NIDDM) patients, and in 25 healthy blood donors. There were no significant differences between the T cell responses of the three groups to tetanus toxoid.