William B. Neaves

Immune privilege in the testis. I. Basic parameters of allograft survival

The fate of solid tissue allografts--skin or parathyroid glands--implanted in the interstitial tissue of the testis was investigated using inbred rats. The results affirm that the testis is an immunologically privileged site despite its efficient lymphatic drainage. Skin allografts survived at least several days longer than orthotopic grafts of similar size, whether major histocompatibility complex (MHC)-compatible or MHC-incompatible, and failed to induce an alloantibody response in most recipients or to prime for secondary antibody responses on rechallenge. Further assessment employed parathyroid grafts that allowed appraisal of their function and its duration, by monitoring serum calcium levels. Most intratesticular MHC-incompatible parathyroids survived for at least twice as long as control grafts in nonprivileged sites, with a median survival time (MST) of 41 days--and one-third of the grafts functioned at 100 days. MHC-compatible grafts fared even better (MST of 60 days), some surviving more than 400 days. Most F1 hybrid grafts survived virtually indefinitely. Splenectomy 5-23 days prior to implantation had a beneficial rather than a detrimental effect on the privilege afforded intratesticular parathyroid allografts. Allograft rejection was accompanied by antibody production in only one-half the animals. Grafts that had undergone functional rejection at the time of recovery usually had an intense mononuclear cell infiltrate, and long-term surviving grafts displayed varying degrees of cellular infiltration among cords of healthy, functional chief cells. Accepted parathyroids were destroyed by active immunization of the host but were unaffected by passively administered alloantibodies. The possible mechanisms controlling graft rejection in this unique privileged site are discussed.

RECONSIDERATION OF THE LYMPHATIC DRAINAGE OF THE RAT TESTIS

An extensive investigation of the lymphatic drainage from the rat testis was carried out in an effort to detect any characteristics which might be important in the immunological privilege the testis extends to allografts. Three different methods revealed a consistent and very efficient lymphatic drainage involving primarily the iliac and renal lymph nodes and to a lesser extent the external lumbar, para-aortic, and posterior gastric nodes. Within minutes, dye or labeled cells injected into the testis could be found within regional nodes. Node hypertrophy was induced by injecting the testes of F1 hybrids with parental strain lymphoid cells (a regional graft-versus-host reaction). Besides indicating that efficient filtration occurs in these nodes, this also established that they are a hospitable environment for cellular immune reactions. Similarly, the capacity of allogeneic cells injected into the testis to induce production of humoral alloantibodies by recipients confirms that exposure to antigens via this route does not in itself suppress immune responsiveness.

The lymphatic drainage of the rat prostate and its status as an immunologically privileged site.

SUMMARY Recent suggestions that the rat prostate is an alymphatic, immunologically privileged site stimulated further investigation of its status using a variety of techniques. Fixation of certain organs by vascular perfusion of glutaraldehyde followed by plastic embedding avoids the distortion and stromal reorganization that often obscures evidence of lymphatic vessels in conventional histological preparations. When applied to the rat prostate, this technique revealed small lymphatic vessels at irregular intervals throughout the sparse stroma. Ink injected into the prostate drained from the organ into iliac lymph nodes within 3 to 4 hr. Enlargement of iliac lymph nodes within 1 week after injection of parental strain lymphoid cells into the prostate of F1 rats confirmed the drainage pattern. Ink and lymphoid cell injections into the bladder wall yielded comparable results, although ink reached iliac nodes sooner than it did in prostate injections. Immunological privilege was investigated by determining survival of skin allografts implanted in the prostate. Skin-into-prostate grafts bearing either major or minor histocompatibility antigens were rejected within a few days of similar orthotopic grafts. The inability of the rat prostate to allow significantly prolonged allograft survival as well as its demonstrated lymphatic drainage argues against an immunologically privileged status.

Regional and subcellular localization of luteinizing hormone releasing hormone in the adult human brain

The localization of luteinizing hormone releasing hormone (LHRH) in the post mortem adult human brain was investigated. LHRH was highly concentrated in medial basal hypothalamic tissue (1.14 ng/mg protein); lower levels of LHRH were present in tissue from the optic chiasm (0.05 ng/mg protein) and mammillary bodies (0.07 ng/mg protein). The concentrations of LHRH in hypothalamic tissue of men and women were similar. LHRH was undetectable (< 0.001 ng/mg protein) in the frontal cerebral cortex and cerebellum. When homogenates of the medial basal hypothalamus were fractionated on continuous or discontinuous sucrose density gradients, LHRH was found to be associated with subcellular particles. Upon examination by transmission electron microscopy, we found that these subcellular particles resembled isolated neuron terminals, i.e., synaptosomes. Low to undetectable amounts of LHRH were found in the cytosol or the myelin + microsome fraction of the gradients. The results of these studies are supportive of the view that LHRH is highly concentrated in neuron terminals of the adult human brain and may, therefore, be a central neurotransmitter or neuromodulator in the human.