Human immune system implanted in mice.
Human immune system immune system
Cells, cell products, organs, and structures of the body involved in the detection and destruction of foreign invaders, such as bacteria, viruses, and cancer cells. Immunity is based on the system's ability to launch a defense against such invaders. implanted in mice
Working separately, two California research groups have accomplished the first successful transplants of the human immune system into mice, providing a potential model for studying AIDS and other diseases without harming humans. "The findings are potentially a very important advance to dissecting the human immune system," says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.
Howard Streicher, an AIDS researcher at the National Cancer Institute in Bethesda, calls the findings "creative, tremendously exciting and potentially useful as a model for AIDS." Scientists had previously infected chimpanzees with the AIDS-causing virus, HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. (SN: 5/23/87, p.331), and researchers in Italy report in the Sept. 22 NATURE that they have infected rabbits with HIV, but so far no animal has been shown to develop AIDS. The California groups are hoping, but have not yet shown, that their newly created mice can develop AIDS.
While both research teams say it was largely the search for an animal model for AIDS that drove them to attempt the recent experiments, they approached the task using different methods. In the Sept. 23 SCIENCE, Irving Weissman, Joseph McCune and their co-workers at Stanford University report transplanting thymus thymus
Pyramid-shaped lymphoid organ (see lymphoid tissue) between the breastbone and the heart. Starting at puberty, it shrinks slowly. It has no lymphatic vessels draining into it and does not filter lymph; instead, stem cells in its outer cortex develop into , liver and lymph-node tissue from human fetuses into mice. (Their findings were released last week, in part to coincide with federal hearings on the use of fetal tissue for research; see page 197, this issue.) The other group, led by Donald Mosier of the Medical Biology Institute in La Jolla, Calif., transferred white blood cells White blood cells
A group of several cell types that occur in the bloodstream and are essential for a properly functioning immune system.
Mentioned in: Abscess Incision & Drainage, Bone Marrow Transplantation, Complement Deficiencies from human adults into mice, as reported in the Sept. 15 NATURE.
But both groups had to overcome the same hurdles: the possibility that the recipient's immune cells would attack the transplant, a reaction called host-versus-graft disease, or the reverse scenario, graft-versus-host disease graft-versus-host disease
A type of incompatibility reaction of transplanted cells against host tissues that possess an antigen not possessed by the donor. Also called graft-versus-host reaction. . They cleared the first hurdle by using a strain of mice, discovered in 1983, with severe combined immunodeficiency Severe Combined Immunodeficiency Definition
Severe combined immunodeficiency (SCID) is the most serious human immunodeficiency disorder(s). It is a group of congenital disorders in which both the humoral part of the patient's immune system and the cells (SCID SCID severe combined immunodeficiency (disease); see under immunodeficiency.
severe combined immunodeficiency
severe combined immunodeficiency disease. ), a genetic disease resulting in a nonfunctional immune system. SCID mice die in the first few months of life, often of infection with Pneumocystis carinii pneumocystis carinii: see pneumonia. bacteria, also a common cause of death in AIDS patients. But SCID mice receiving the experimental transplants do not develop the infection--the first indication that the transplants work. Weissman reports transplanted mice living for 16 months; Mosier says his transplanted mice have lived for eight months.
To overcome the second hurdle, Weissman's team used fetal tissue, which is too immature to mount an immune response immune response
An integrated bodily response to an antigen, especially one mediated by lymphocytes and involving recognition of antigens by specific antibodies or previously sensitized lymphocytes. against the host. Although Mosier's group performed transplants with adult human cells -- already immunologically "knowledgeable" -- the cells caused only mild symptoms of graft-versus-host disease in the mice, a result Mosier says he cannot explain entirely but plans to investigate.
Further proof of the transplant's success for both groups came with detailed biochemical and immunological experiments. Weissman's group demonstrated that the transplant tissues function in mice as they would in human fetuses, where immature immune cells from the liver normally pass through the thymus and lymph nodes Lymph nodes
Small, bean-shaped masses of tissue scattered along the lymphatic system that act as filters and immune monitors, removing fluids, bacteria, or cancer cells that travel through the lymph system. , exiting as mature immune cells ready to attack invading microorganisms and toxins. In mice, the group found cells from the transplanted human liver in the transplanted thymus and lymph-node tissue, and, later, as mature immune cells in the circulating blood. After four to six weeks, the numbers of these immune cells begin to decrease, the team reports.
Mosier says his results indicate that a single injection of the human immune cells reconstitutes the ability to respond to antigens for the life of the SCID mouse receiving the transplant. To test transplanted cells' ability to function immunologically, his group injected tetanus toxin tetanus toxin
The neurotropic exotoxin of Clostridium tetani that causes tetanus. into mice transplanted with blood cells blood cells,
n.pl the formed elements of the blood, including red cells (erythrocytes), white cells (leukocytes), and platelets (thrombocytes).
See erythrocyte and leukocyte. Platelets are classed separately. from human adults previously immunized for tetanus. Eight of the 10 immunized mice produced antibodies to the toxin, they report. Mosier's group also has observed that transplanting mice with human cells containing Epstein-Barr virus Epstein-Barr virus (EBV), herpesvirus that is the major cause of infectious mononucleosis and is associated with a number of cancers, particularly lymphomas in immunosuppressed persons, including persons with AIDS. leads to tumors in the mice, a finding that provides a potential model for studies of this virus.
Weissman says his technique, too, paves the way for studying other diseases. For example, transplanting pancreatic tissue into SCID mice may provide a system for investigating the malfunctions leading to diabetes, he says. A project already underway in Weissman's lab involves isolating human stem cells, the precursor cells to the entire immune system. Weissman recently reported isolating mouse stem cells (SN: 7/9/88, p.20).
Mosier's and Weissman's findings are equally important and will both lead to advances in medicine, say researchers familiar with their work. "The systems are not competitive," says Weissman. "They are two pieces of a great big pie just beginning to be understood."