T-cell growth factor and method of making same

Details T-cell growth factor and method of making same T-cell growth factor and method of making same

1983-01-25

1986-11-18

Warren, Charles F.

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Enzymatic production of a protein or polypeptide

435240, 435241, 435948, 935 34, C12P 2100, C12N 500, C12N 502, C12R 191

Patent

active

046236228

DESCRIPTION:

BRIEF SUMMARY
The immune protects the body from a myriad of "foreign" invaders--bacteria, fungi, viruses, and parasites-as well as internal invaders--cancer cells. Two important components of the immune system are B-lymphocytes (antibody producers) and T-lymphocytes. The T-lymphocytes function as regulators and effectors in protecting the body against foreign maladies. T lymphocytes can function as helper cells, killer cells, or suppressor cells. Helper cells cooperate with B lymphocytes for antibody production or with generating other T cell responses. Killer T cells can eliminate virus infected cells and cancer cells or reject foreign grafts. Suppressor T cells serve to shut down responses thus preventing "over reaction". T lymphocytes can function as cells or through the release of soluble factors (cytokines) specifically known as lymphokines. See DeWeck, A. L. "Lymphokines, monokines, and cytokines: an increasingly valuable object for studies in molecular immunology", Molecular Immunology 17: 535-537, 1980.
An antigen is a substance which is capable, under appropriate conditons, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes (or their products), or both. Antigens may be soluble substances, such as toxins and foreign proteins or polysaccharides, lipids and nucleic acid, or particulate, such as bacteria and tissue cells; however, only the portion of the foreign molecule known as the antigenic determinant combines with antibody or a specific receptor on a lymphocyte.
An antibody is an immunoglobulin molecule that has a specific amino acid sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it. Antibodies are classified according their biochemistry and to their mode of action as agglutinins, bacteriolysins, hemolysins, opsonins, precipitins, etc.
Cell mediated immunity refers to the specific acquired immunity in which the role of small lymphocytes of thymic origin (T-lymphocytes) is predominant; it is responsible for resistance to infectious diseases caused by certain bacteria, fungi, and viruses, certain aspects of resistance to cancer, delayed hypersensitivity reactions, certain autoimmune diseases, and allograft rejection, and plays a role in certain allergies.
Lymphokines are important mediators of biological responses; not only are immune responses regulated by these molecules but other physiological systems are influenced and affected by them. The study of lymphokines is at present extremely important for a better understanding of regulatory functions in the immune system and other systems in health and disease. The biological characterization of lymphokines is still in its preliminary stages. This is primarily due to the small amount of lymphokines produced in in vitro systems. These substances are active at extremely low physiologic concentrations. Furthermore, when dealing with crude lymphokine preparations there are antagonistic factors, different molecules which have the same biological activity or one molecule having several activites--all of which interfere with bioassays to define specific lymphokine function.
Therefore, there is a need for large-scale lymphokine production in pure form to facilitate the study of these important molecules. The use of cloned leukemic cell lines may provide the link needed for increasing our understanding of the cellular mechanisms of lymphokine production, the interaction of these molecules with target cells, and the isolation and biochemical characterization of individual lymphokines for research and clinical use.


INTRODUCTION TO INVENTION

Leukemic cell lines have provided a wealth of information regarding our understanding of lymphocyte differentiation and maturation. See Minowada, J. "Markers of human leukemia-lymphoma cell lines reflect hematopoietic cell differentiation." Human Lymphocyte Differentiation: Its Application

REFERENCES:
J. Immunol., 128: 1122 (1981) Mier et al, "The Purification and Properties of Human T Cell Growth Factor".
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J. Immunol., 126: 1351 (1981), Caplan et al, "Properties of Sodium Dodecyl Sulfate-Denatured Interleukin 2".
Farrar et al, "Mouse and Human T Cell Line-Derived Interleukin-2", Lymphokines, vol. 5, pp. 353-370 (1982).
Prog. Allergy, 26: 137-238 (1979) Kindred, "Nude Mice In Immunology".
Molecular Immunology, 17: 535-537 (1980) Deweck, "Lymphokines, Monokines and Cytokines: an Increasingly Valuable Object for Studies in Molecular Immunology".
Nature, 284: 278 (1980) Wagner et al, "T-Cell Derived Helper Factor Allows in vivo Induction of Cytotoxic T Cells in nu
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Human Lymphocyte Differentiation: Its Application to Cancer, (1978), Minowada, p. 337, "Markers of Human Leukaemia-Lymphoma Cell Lines Reflect . . . ".
Immunol. Rev., 51: 337 (1980) Smith, "T-Cell Factor".
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This invention was supported by grants from the National Cancer Institute (Ca 18734) and the National Institute on Child Health and Human Development (HD 02080). The HSB-2 ERICR and HAT sensitive HSB-2-ERICR cell lines were deposited on Jan. 21, 1983 at the American Type Culture Collection Depository, 12301 Parklawn Drive, Rockville, Md. 20852 and identified by the deposit numbers CRL 8198 and CRL 8197, respectively.

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