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Biomedical subjects

T L Feldbush

Publications and source records attributed to T L Feldbush.

At least 37 records · Page 2Linked to original sources

The effect of growth hormone and insulin upon MLC responses and the generation of cytotoxic lymphocytes.

The ability of growth hormone (GH) and insulin to influence positively T lymphocytes responding to an alloantigen stimulus in vitro was analyzed through the use of a serum substitute system. The presence of insulin but not GH, enables the generation of a successful mixed lymphocyte culture (MLC) blastogenic response. However, the presence of GH during a 5-day MLC allowed for the generation of cytotoxic T lymphocytes (CTL). It was further demonstrated that GH needed to be present during the first 2 days of the culture system, presumably before the entry of the precursor CTL into cell division. The results are discussed in terms of the induction, by the GH, of ornithine decarboxylase activity and how this might relate to the successful generation of CTL activity.

Animals↗

Role of T cells in the development of memory B cells. Quantitative and qualitative analysis.

The purpose of this investigation was to address the current controversy regarding the T-cell requirement for the generation of B-memory cells. We have circumvented the possible objection to previous experiments regarding residual T cells in T-deprived animals by examining memory cell generation in relation to the numbers of T cells participating in the immune response. Thymectomized and lethally-irradiated rats were reconstituted with foetal liver or a more mature stem cell source, neonatal liver. These animals were given graded doses of purified T cells one day before immunization with alum-precipitated DNP-BGG + Bordetella pertussis. Four weeks after priming, cell suspensions from experimental groups were adoptively transferred to carrier primed recipients and challenged with DNP-BGG in saline to assess memory cell development. The data demonstrate that in the absence of T cells only minimal memory development occurred. However, when T cells were present, the level of memory cell development increased with increasing numbers of T cells. By examining the relative affinity of the antibody produced in the primary and secondary responses, the increase in memory cell development in relation to increased numbers of T cells was shown to be due to the selective generation of high affinity memory B cells.

Animals↗

In vitro antigen-mediated clonal expansion of memory B lymphocytes.

An in vitro model for the propagation and expansion of the memory B lymphocyte population is described. DNP-BGG immune cells were mixed with OVA immune cells and challenged immediately with DNP-OVA. After the 1st response had begun to wane, the cells were rechallenged with DNP-OVA (day 11 of culture). An average of 13-fold more PFC were observed after delayed challenge (day 11). This expansion in the PFC response was an antigen-dependent process and did not involve recruitment of new memory cells from the virgin lymphocyte pool. The level of expansion of the memory cell pool was also calculated using limiting dilution analysis and was found to fall in a range of 16- to 67-fold increase in precursor frequency. In addition to the expansion of the memory B cell population, we also observed the development of 2 immunoregulatory cycles previously observed only in vivo. First, in the presence of persistent antigen, a cyclical PFC response was seen. Second, after day 10 of culture, optimal PFC numbers were observed only when DNP-lysine was added to the plaque assay. Such hapten-augmentable PFC responses have been reported by other investigators as indicative of anti-idiotypic regulation. This possibility is examined more extensively in the following communication.

Animals↗

The third component of complement inhibits human lymphocyte blastogenesis.

Purified human C3 was studied for its ability to regulate human peripheral blood lymphocyte activation in a serum-free tissue culture system. C3 and its fragments formed by trypsin digestion were not mitogenic. However, C3 inhibited both mitogen- and antigen-induced lymphocyte proliferation in a dose-related manner. The observed inhibition by C3 increased with an increase in the dose of mitogen, with 50% inhibition seen at a C3 dose of 2.5 to 25 microgram/ml. Inhibition was induced even when C3 was added at 69 hr in a 99-hr culture, suggesting an effect on late events in activation. The inhibition was not mediated through generalized cytotoxicity, was not an artifact of kinetic alteration and still occurred in macrophage-depleted cultures. A small m.w. fragment of C3 which contained the inhibitory capacity in our C3 preparation was similar to C3a in size, anaphylatoxin activity, heat and acid stability and inhibition by serum. Our results indicate that cleavage products by C3 may play a negative role in lymphocyte activation.

Blood↗

The role of insulin in the response of murine T lymphocytes to mitogenic stimulation in vitro.

The ability of insulin to influence the responsiveness of murine T lymphocytes in a culture system containing a serum substitute was documented. The presence of insulin was found to enhance the concanavalin A (Con A) reactivity of the lymphocytes. Once the cells were activated by a short-term exposure to Con A, insulin was capable of replacing Con A for the continued stimulation of the cells. This was true both for lymphocyte proliferation and for the generation of nonspecific cytotoxic T lymphocytes. The presence or absence of insulin was not found to influence the phytohemagglutinin responsiveness of the T lymphocytes. Possible reasons for the observed results are discussed in relation to a proposed model for lymphocyte activation.

Animals↗

Studies on a weakly immunogenic squamous cell carcinoma of the rat prostate.

Different methods were tested to elicit and assess transplantation immunity against the weakly immunogenic 11095A squamous cell carcinoma, a methylcholanthrene-induced prostatic tumor of the inbred F344 rat strain. The results described emphasize the difficulty with which effective immune responses are induced by very weak transplantation antigens. The importance of using poorly immunogenic tumors as research models is discussed.

Animals↗

T- and B-cell distribution in pregnancy.

We established the percentage of thymus-derived lymphocytes associated with cellular immune responses and bone marrow-derived, antibody-producing cells in maternal blood throughout normal gestation. The data are in conflict with a recent proposal that reversal ot the T:B cell ratio associated with the serum human chorionic gonadotrophin peak of early pregnancy assists in fetoplacental allograft acceptance. Moreover, variability on lymphocyte dynamics in four women followed up serially throughout pregnancy, as well as T- and B-cell determinations in 15 patients whose pregnancy complications are potentially related to maternal-fetal immunologic aberrations, suggests that more sensitive immunologic methods of monitoring the host immune response are necessary to be clinically useful in obstetrics.

Adolescent↗

Immunostimulation by cryosurgery: an orthotopic model of prostate and bladder cancer in the rat.

In patients with prostate cancer, cryosurgery has been highly effective in eradication of the primary tumor. Certain clinical observations have suggested the presence of an additional systemic anticancer effect, presumably immunologic in nature, but proof is lacking. To study this problem further, we developed two animal tumor models. Instead of using the classical subcutaneous site, we transplanted the 11095A and R-3327 prostate tumors into rat prostate, the 4909 bladder tumor into rat bladder. In these respective orthotopic locations, the 3 tumors displayed favorable growth characteristics with good accessibility for cryosurgery. This model should be considered for studies involving any localized treatment of an established urologic tumor.

Adenocarcinoma↗

Rat prostate carcinoma 11095-A: profile of organ- and tumor-specific antigens.

The 11095-A squamous cell tumor is a transplantable prostate carcinoma of the F344 rat. No tumor-specific antigens could be demonstrated for this carcinoma by serologic tests or in host protection experiments. Preliminary data from two other assay systems indicate that tumor-specific antigens may be weakly expressed in this model.

Animals↗

R3327 adenocarcinoma of the Copenhagen rat as a model for the study of the immunologic aspects of prostate cancer.

The Dunning R3327 prostate adenocarcinoma of the Copenhagen rat was developed as a suitable model of human prostate cancer. Inoculation of tumor tissue mince or cells sc in the flanks of recipient rats produced tumors that had the macroscopic and microscopic characteristics of the human disease. The histologic picture of these tumors was that of a well-differentiated adenocarcinoma with the formation of glands and acid secretions within the acini. Tumors were also produced in the dorsolateral lobe of the prostate by the injection of cells. The intraprostate tumor, although initially confined to the injected lobe, grew to involve the surrounding tissues and eventually metastasized to the lymph nodes and lungs. Occasional metastatic lesions were found in other organs also. Acid phosphatase could be domonstrated by histochemical staining of frozen tumor sections, and elevated levels of the enzyme were seen in the sera of rats bearing long-term subcutaneous tumors. During investigation of the tumor, a fast-growing tumor line arose that grew equally as well in females as in males. The histology of this tumor was that of an undifferentiated anaplastic tumor.

Acid Phosphatase↗