B & T AIDS patients hold the Mayo

New data show that B cells can help reconstitute compromised immune systems by stimulating T cell production

By Owen Dyer

There may be a way back for even the most damaged immune system, if recent discoveries in mice hold true in humans. Rochester, Minnesota Mayo Clinic researchers found that, contrary to accepted wisdom, two key components of the immune system, T and B cells, don't develop independently. Applying their newfound knowledge, they were able to fire up new T cell growth in immunosuppressed mice. Reproducing the effect in humans could have dramatic implications for immunodeficiency diseases such as AIDS and cancer.

The research team, led by Drs Marilia Cascalho and Jeffrey Platt, reports in the April 15 issue of the Journal of Immunology that B cells, the lymphocytes that produce antibodies, help to generate T cells, the lymphocytes that fight viruses and tumours.

"Previously, it was thought that B cells and T cells, two components of immunity produced by the lymphatic tissues, develop independently until they eventually came together to fight microbes or to eliminate infected cells in the body," says Dr Cascalho. "Now we know that the B cells and the immunoglobulin that they produce can help reconstitute immunity by promoting the development of T cells."

A strong immune system requires not just a large number of T cells but also a large variety. T cell diversity tends to fall off in patients with AIDS or other immunodeficiency diseases, and those undergoing cancer chemotherapy. When the researchers transferred B cells or gamma globulin, a fraction of blood teeming with antibodies, from normal mice to those with limited T cell diversity, they found that the thymus generated new T cells with more variety.

"By understanding how the body produces T cell diversity in this way, we believe it may have direct impact on many patients whose immune defences have been compromised," says Dr Platt. "Before, we knew of no way that this part of the immune system could build itself back up. Now, we think that this is a way."

The authors also speculate that gamma globulin might counter autoimmunity. In some cases autoimmune diseases such as arthritis arise because the body lacks the diverse T cells needed to control immune responses. New T cells promoted by gamma globulin could control the overreacting T cells that attack the body's healthy cells. In this way, clinicians may be able to alter immunity by skewing or redirecting the focus of the body's misdirected immune response. However, this theory remains untested.

The group is eager to put its findings to the test in human clinical trials. Since gamma globulin is approved by the US FDA for other uses, this process may take less time than usual. "Because of this availability, we should expect to see some results in a matter of a few years, rather than in a decade or more," says Dr Cascalho.

Finally, the researchers want to discover whether all or only part of the immunoglobulin molecule is essential to trigger T cell production. If they can identify the critical portion of the molecule, it might be manufactured alone at less cost than expensive fully constituted human immunoglobulin.