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.