CD4 T Cells and TH1TH2 Balance Plays an Important Role in Autoimmunity in Some Animal Models

Autoimmune T-cell clones have been obtained from all of the animal models listed in Table 20-2 by culturing lymphocytes from the autoimmune animals in the presence of various T-cell growth factors and by inducing proliferation of specific autoimmune clones with the various autoantigens. For example, when lymph-node cells from EAE rats are cultured in vitro with myelin basic protein (MBP), clones of activated T cells emerge. When sufficient numbers of these MBP-specific T-cell clones are injected intravenously into normal syngeneic animals, the cells cross the blood-brain barrier and induce demyelination; EAE develops very quickly, within 5 days (see Figure 20-7).

A similar experimental protocol has been used to isolate T-cell clones specific for thyroglobulin and for M. tuberculosis from EAT and AA animals, respectively. In each case, the T-cell clone induces the experimental autoimmune disease in normal animals. Examination of these T cells has revealed that they bear the CD4 membrane marker. In a number of animal models for autoimmune diseases it has been possible to reverse the autoimmunity by depleting the T-cell population with antibody directed against CD4. For example, weekly injections of anti-CD4 monoclonal antibody abolished the autoimmune symptoms in (NZB X NZW) F1 mice and in mice with EAE.

Most cases of organ-specific autoimmune disease develop as a consequence of self-reactive CD4+ T cells. Analysis of these cells has revealed that the TH1/TH2 balance can affect whether autoimmunity develops. TH1 cells have been implicated in the development of autoimmunity, whereas, in a number of cases, TH2 cells not only protect against the induction of disease but also against progression of established disease. In EAE, for example, immunohistologic studies revealed the presence of Th1 cytokines (IL-2, TNF-a, and IFN-7) in the central nervous system tissues at the height of the disease. In addition, the MBP-specific CD4+ T-cell clones generated from animals with EAE, as shown in Figure 20-7, can be separated into TH1 and TH2 clones. Experiments have shown that only the TH1 clones transfer EAE to normal healthy mice, whereas the TH2 clones not only do not transfer EAE to normal healthy mice but also protect the mice against induction of EAE by subsequent immunization with MBP plus adjuvant.

Experiments that assessed the role of various cytokines or cytokine inhibitors on the development of EAE have provided further evidence for the different roles of TH1 and TH2 cells in autoimmunity. When mice were injected with IL-4 at the time of immunization with MBP plus adjuvant, the development of EAE was inhibited, whereas administration of IL-12 had the opposite effect, promoting the development of EAE. As noted in Chapter 12, IL-4 promotes development of TH2 cells and IFN-7, in addition to other cytokines such as IL-12, promotes development of TH1 cells (see Figure 12-12). Thus, the observed effects of IL-4 and IL-12 on EAE development are consistent with a role for TH1 cells in the genesis of autoimmunity.

Was this article helpful?

0 0
Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

Get My Free Ebook

Post a comment