Thomas F. Dougherty

Effect of Pituitary Adrenotropic Hormone on Lymphoid Tissue.

Summary Injection of pure pituitary adrenotropic hormone into CBA strain mice produces a decrease in weight of the inguinal, axillary and mesenteric nodes, and of the thymus. The spleen did not show a weight decrease.

THE ROLE OF LYMPHOCYTES IN NORMAL AND IMMUNE GLOBULIN PRODUCTION, AND THE MODE OF RELEASE OF GLOBULIN FROM LYMPHOCYTES

The inverse relationship between the degree of adrenal cortical secretion and thymic sizel-l led to studies to determine whether this relationship extended to other lymphoid structures. The secretion of adrenal cortical hormones controlled by the pituitary adrenotrophic hormone is the normal mechanism regulating lymphoid tissue mass.s* Further, a t a time when lymphoid tissue involution is maximal, as a result of augmented pituitary-adrenal cortical secretion, a profound absolute lymphopenia is present.lo The diminished lymphoid tissue mass, occurring concomitantly with blood lymphopenia, posed the problem of explaining this apparently paradoxical phenomenon. In other words, it was necessary t o explain why lymphocytes disappeared from both lymphoid organs and from the blood a t approximately the same time. An answer to this problem was sought in detailed histological study of lymphoid structures, at a time when lymphoid tissue involution and blood lymphopenia were most marked. Earlier studies had shown that there was no accumulation of lymphocytes in large capillary beds which would account for their disappearance from the blood. The histological studies revealedlls l2 that the decrease in lymphoid tissue mass and the blood lymphopenia were both a result of the marked dissolution of lymphocytes which occurred in the lymphoid organs as a consequence of augmented pituitary-adrenal cortical secretion. Therefore, decreased lymphoid tissue weight was due to fewer lymphocytes in the lymphoid organs, and the lymphopenia was a result of failure of delivery or disintegration of these cells.

The Demonstration of Antibodies in Lymphocytes.

Summary Agglutinin and hemolysin titers have been obtained from extracts of washed cells secured from selected lymph nodes and thymi of mice immunized to sheep erythro-cytes. The titers of similar extracts of salivary glands and muscle of the same immunized animals were negative in all dilutions although these extracts were higher in nitrogen content. Per unit of extractable nitrogen, lymphoid tissue had significantly higher agglutinin and hemolysin titers than did the sera of the same animals. It is concluded that antibodies are concentrated in lymphocytes.

Pituitary-Adrenal Cortical Control of Antibody Release from Lymphocytes. An Explanation of the Anamnestic Response.

Summary An anamnestic reaction has been produced in rabbits and mice following a single injection of adrenal cortical extract or pituitary adrenotrophic hormone. Desoxycorticosterone acetate injection failed to elicit this response. In adrenalectomized mice the anamnestic reaction also was elicited by adrenal cortical extracts but not by adrenotrophic hormone, despite the demonstrated presence of antibodies in the lymphocytes of these animals. Therefore, adrenal cortical mediation is essential for control of the release of antibody from lymphocytes. Two toxic stimuli, benzene and potassium arsenite, liberated antibodies from lymphocytes in intact mice. These stimuli failed to effect this release in adrenalectomized mice. The data establish the role of pituitary-adrenal cortical secretion as the controlling mechanism for the release of antibody from lymphocytes. The anamnestic reaction is one manifestation of this control.

Relationship of the Effects of Adrenal Cortical Secretion on Lymphoid Tissue and on Antibody Titer.

Summary Agglutinin titers to sheep erythrocytes are enhanced as a result of adrenal cortical extract injection. Titers were increased within 6 hours after a single injection of adrenal cortical extract into hyper-immunized rabbits. Increased titers produced by a single injection of adrenal cortical hormone return in 24 hours almost to levels existing before hormone administration. Continued hormone injection maintained elevated titers for 2 weeks.

Influence of Pituitary Adrenotrophic Hormone on Lymphoid Tissue Structure in Relation to Serum Proteins.

Summary Decrease of lymphocytes in lymphoid tissue and the concomitant lymphopenia following injection of pituitary adrenotrophic hormone, or adrenal cortical extract, are in their time relationships correlated with an increase in serum proteins. These same relationships persist in animals given daily injections of adrenotrophic hormone. Adrenalectomized mice, in which hemoconcentration is prevented, have a lower than normal concentration of serum proteins for at least 8 days following operation.

Acceleration of lymphoid tissue regeneration in x-irradiated CBA-W mice by injection of thymosin.

Thymosin, a lymphocytopoietic preparation obtained from calf thymus, was examined for its effect on the rate of regeneration of lymphoid tissue in CBA/W mice exposed to whole body x-irradiation. In...

Relationship of Antibody Content of Normal and Malignant Lymphocytes.

Summary Staphylococcus antitoxin titers have been obtained from extracts of lymphocytes secured from a rapidly growing mouse lymphosarcoma. Comparison of these titers with those of the sera and normal lymphocytes of the same animals suggested that tumor tissue had a slightly higher antibody content. Tumor cells were capable of obtaining antibody from some other source in the body, presumably normal lymphocytes. The growth of an antibody-containing tumor transplant in normal mice was accompanied by the development of antibody-containing malignant cells. The normal lymphocytes of the host animal receiving this transplant contained antibody. There is a reversible exchange of antibody protein between normal and malignant lymphocytes.