T Cell Vaccination

Irun R Cohen, Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel

T cell vaccination (TCV) is a term describing a method for modulating immune responses in which T cells are administered as immunogenic agents. Typically, an autoimmune response is the subject for modulation and the vaccine consists of T cells specifically reactive to the target autoantigen. The first example of TCV in an autoimmune disease was reported in 1981 by Ben-Nun, Wekerle and Cohen who treated Lewis rats with a line of Lewis rat CD4+8" T cells specifically reactive to the dominant epitope of myelin basic protein (MBP). The anti-MBP T cells, which served as the vaccine, were irradiated (1500 R) to prevent them from attacking the recipients and producing experimental autoimmune encephalomyelitis (EAE). Vaccination with the attenuated anti-MBP T cells led to resistance to later attempts to induce EAE by active immunization to MBP in adjuvant. Subsequently it was shown that TCV could also induce resistance to EAE adoptively transferred by virulent anti-MBP T cells.

T cell vaccination was extended to other disease models (adjuvant arthritis (AA), collagen-induced arthritis, experimental autoimmune neuritis, experimental autoimmune thyroiditis and insulin-depen-dent diabetes mellitus (IDDM)). Moreover, TCV was found to abort established autoimmune disease (AA, IDDM) and spontaneous autoimmune disease (IDDM) and so can be viewed as therapy as well as prevention.

The term TCV was coined to describe manipulation of autoimmune responses using autoimmune T cell vaccines; however, in principle and in practice the procedure may be applied to modify undesirable T cell responses central to allograft rejection or to allergy.

The concept of vaccination was introduced by Jenner about two centuries ago to describe the use of cowpox to induce immunity to smallpox. A century later, Pasteur extended the word to encompass the concept of using an attenuated infectious agent of disease to induce resistance (now understood to be immunological) to virulent forms of the agent. TCV represents a further extension of Pasteur's vaccination concept to include the individual's own lymphocytes as perpetrators of disease from which vaccines might be made.

T cell vaccination may be analyzed conveniently by dividing the subject into three parts: the T cell vaccine, the regulatory response to the vaccine, and the lymphocyte networks linking these T cells.

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