T-lymphocytes are designated as such because they are derived from or influenced by the thymus hormone. To become mature, all T-lymphocytes must reside in the thymus gland for a period of time. The cell in the thymus gland is called a thymocyte, and acquires either CD4 or CD8 characteristics. The CD classification is given to further differentiate the types of T-lymphocytes. During the maturation period within the thymus gland, T-lymphocytes eventually become either CD4 cells or CD8 cells.
Only those thymocytes expressing CD4 or CD8 characteristics are positively selected to emigrate, by way of the thymus gland, to the lymphatic system. This differentiation process results in mature lymphocytes that can recognize foreign bodies, viruses or cancerous cells, in the context of major histocompatible complex hormones. (Histocompatibility refers to the ability of the cells of one tissue to exist in the presences of cells of another tissue, such as would be the case in a graft or transplant.) Thus, CD4 cells are known as "helper" cells because they "help" the immune system by recognizing foreign substances on contact. CD8 cells are called T-suppressor/cytotoxic or "killer" cells. They require histocompatible expression on target cells
to be activated.
Studies have identified at least six types of thymic cells. These particular cells produce interleukin-1 (IL-1), interleukin-4 (IL-4), interleukin-6 (IL-6), thymosin, thymopoietin, and thymulin. These hormones, or proteins, secreted by the thymus gland are found to have an effect on T-lymphocyte differentiation and activation. Of these thymic hormones thymosin, thymulin and thymopoietin in thymic humoral factor, may possibly reach the circulation and act on the lymphocytes and tissues at various sites in the human body.
One of the central questions remaining in thymic biology is how to define the actual role of these hormones. Do they conduct only intrathymic activities? Or are they secreted by the thymus gland to act on lymphocytes or tissues in other parts of the human body? Or, might they do both?
If the thymus gland is a hormone-secreting tissue, then alterations in its structure and function should be demonstrated when there exists certain endocrine (hormonal) imbalances. Examples might be lack of growth hormone or lack of sex hormone in an individual. Congruously, the function of other tissues may be altered by the presence or absence of thymic hormones. Both types of interactions have been studied, recognized and proven, suggesting interactive regulatory pathways between the thymus gland and the other endocrine structures.
Pierpaoli, an early pioneer in thymus gland research, and his co-workers, are among the first to identify dependency of the central nervous system's development on thymus gland function. Other studies have established an important interaction between the thymus gland and the development of the pituitary gland in the brain.
The age-related deterioration of learning and memory abilities has also been linked to the atrophy, or wasting away, of the thymus gland. However, the mechanism underlines that the effect of the thymus gland on the central nervous system's cognitive dysfunction is still unknown at this time. Test results may reveal a reduction in thymic hormone activity, as well as the subsequent deterioration of the immune system, may induce a deficit in the central nervous system's cognitive function.
In addition to the central nervous system, the thymus gland may also affect functions of other endocrine, (hormonal) tissues.
Congenital (from birth) absence of the thymus gland is associated with alterations of the pituitary gland, adrenal gland, thyroid and ovaries. Antithyroid drugs that induce hypothyroidism (decreased activity of the thyroid gland) also cause a marked atrophy of the thymus gland. T-4 is one type of thyroid hormone. When its levels were reduced following antithyroid drug medication treatment, the thymocyte population in the thymus gland was also reduced. Conversely, when T-3--a different type of thyroid hormone--was administered in mice, multiple facilitated effects on thymus function were produced. Those effects included increased weight and cell population as well as enhanced thymocyte production. Within thirty days after surgery, removal of the pituitary gland resulted in a fifty percent reduction in both thyrnic gland weight and the concentration of the thymic hormone known as thymosin.
During the last twenty years, at least four separate and distinct thymus preparations have been isolated and analyzed for T-lymphocyte-regulating properties. Thymosin, thymulin, thymopoietin and thymic humoral factor (THF) have all been utilized as thymic hormonal preparations for hormone replacement therapy.
Thymosin (TF) is a group of low molecular-weight proteins extracted from bovine, or cow, thymus. Thymosin has displayed potent stimulatory effects on T-lymphocyte-mediated immunity. It increased lymphocyte activity and enhanced IL-6 production in spleen cells. (IL-6, or interleukin-6, is a protein made by the lymphocyte.)
Thymosin had a stimulating effect on luteinizing hormone and gonadotropin releasing hormone, both pituitary hormones, in (in vivo) studies of pituitary tissues. The release of another pituitary hormone known as prolactin, as well as human growth hormone and adrenal corticotropin (ACTH) are increased by (in vitro) thymosin studies. Luteinizing hormone was not increased by thymosin in vitro.
Thymulin is a protein extracted from porcine (pig) thymus tissue. It affects the differentiation of immature bone marrow cells in the function of T-lymphocytes. This thymic hormone stimulates CD8 "killer" cell lymphocyte activity in the spleen cell cultures obtained from old, but not young, mice. The serum level of thymulin decreases with age, and it coincides with thymus atrophy.
Thymulin requires zinc for full biological activity. Patients who suffer from Crohn's Disease (a type of autoimmune intestinal disease) or acute lymphobiastic leukemia are zinc deficient. They also have a reduction in thymulin activity. All young and old rats had increased circulation thymulin levels in response to administration of growth hormone and thyroid hormone injections.
THYMIC HUMORAL FACTOR (THF)
Thymic humoral factor is an extract of calf thymus. Interleukin-2, also known as IL-2, is a protein manufactured by lymphocytes. It was enhanced by the influence of THF in spleen cell cultures. Peripheral blood obtained from patients with chronic hepatitis B and viral infections responded to THF with increased production of IL-2. This suggests a possible antiviral role for this thymic hormone, and is one of the reasons we should replace thymic hormone as we pass the second decade.
THYMOPOIETIN (AND THYMOPENTIN)
Thymopoietin is a protein isolated from bovine (cow) thymus gland. It thoroughly enhances T-lymphocyte differentiation and the effect of function on mature T-lymphocytes. Thymopentin is a protein derivative of thymopoietin; however, it has its own distinct biological properties.
Various studies suggest that the thymus gland and thymic hormones contribute to human immunity, the neuroendocrine system, the reproductive system, and the development of the central nervous system. Additionally, alteration in the status of the thyroid, adrenal and pituitary glands, as well as the kidney, have affected the structure and function of the thymus gland.
Results indicate that the presence of thymic hormone in circulation can have an effect on a variety of other organ systems. All four thymic preparations now available commercially are identified, thus far, as previously stated. Therefore, it is advisable to replace thymus hormones with those presently available preparations. Such a replacement therapy is totally harmless. The Food and Drug Administration has not regulated thymic hormones because they are not yet considered drugs or pharmaceuticals. Thymus hormone is in the same status and classification as DHEA and melatonin hormones, which are available over the counter.