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S Ansar Ahmed

Publications and source records attributed to S Ansar Ahmed.

At least 19 recordsLinked to original sources
PubMed2006

Estrogen selectively regulates chemokines in murine splenocytes.

Estrogen has striking effects on immunity and inflammatory autoimmune conditions. One potential mechanism of estrogen-induced regulation of immunity and inflammatory autoimmune conditions is by altering the secretion of chemokines by lymphocytes, an aspect not well addressed thus far. We found that estrogen has marked, but differential, effects on the secretion of chemokines from activated splenocytes. Estrogen treatment significantly increased the secretion of MCP-1, MCP-5, eotaxin, and stromal cell-derived factor 1beta from Con A-activated splenocytes when compared with placebo-treated controls, and it had no effects on the levels of RANTES, thymus and activation-regulated chemokine, and keratinocyte-derived chemokine (KC) at 24 h. A kinetic analysis showed that chemokines tended to increase with stimulation time, but only MCP-1 and MCP-5 showed a biological trend of increasing in splenocytes from estrogen-treated mice, and KC was decreased significantly in estrogen-treated splenocytes at 18 h. Estrogen did not affect the protein levels of chemokine receptors CCR1 or CCR2 at 24 h. Estrogen-induced alterations in the levels of MCP-1 and MCP-5 are mediated, in part, by IFN-gamma, as estrogen treatment of IFN-gamma null mice, unlike wild-type mice, did not up-regulate these chemokines. However, addition of recombinant IFN-gamma resulted in markedly increased secretion of MCP-1 and MCP-5 only in the cells derived from estrogen-treated mice. These studies provide novel data indicating that estrogen may promote inflammatory conditions by altering the levels of chemokines, providing evidence for an additional mechanism by which estrogens can regulate inflammation.

Animals↗
PubMed2006

IFN-gamma-inducing transcription factor, T-bet is upregulated by estrogen in murine splenocytes: role of IL-27 but not IL-12.

Estrogen is believed to be involved in regulation of the differentiation, survival, or function of diverse immune cells as well as in many autoimmune and inflammatory diseases. However, the mechanisms behind the immunomodulatory effects of estrogen are poorly understood. Previously, we have shown that natural estrogen can upregulate IFN-gamma and IFN-gamma-mediated-inflammatory events (iNOS, nitric oxide, COX-2). Since IFN-gamma is regulated by T-bet, in this study, we investigated whether estrogen induces T-bet expression in primary murine splenocytes. We found that in vivo estrogen treatment primes splenocytes for early upregulation of T-bet upon activation by T cell stimulants, Concanavalin-A (Con-A) or anti-CD3 antibodies. The expression of T-bet protein was not altered by IL-12 while IFN-gamma had partial effects on T-bet in splenocytes from estrogen-treated mice. Notably, T-bet expression increased in Con-A-activated splenocytes from estrogen-treated mice in the presence of IL-27. Together, our studies show that in vivo estrogen exposure primes lymphocytes towards Th1 type development by promoting/upregulating T-bet expression, which is upregulated in part by IFN-gamma and IL-27. Given that T-bet is a potent inducer of IFN-gamma, these studies may lead to new lines of investigation in relation to many female-predominant autoimmune diseases and inflammatory disorders.

Animals↗
PubMed2006

Estrogen regulation of nitric oxide and inducible nitric oxide synthase (iNOS) in immune cells: implications for immunity, autoimmune diseases, and apoptosis.

Nitric oxide plays a central role in the physiology and pathology of diverse tissues including the immune system. It is clear that the levels of nitric oxide must be carefully regulated to maintain homeostasis. Appropriate levels of nitric oxide derived from iNOS assist in mounting an effective defense against invading microbes. Conversely, inability to generate nitric oxide results in serious, even fatal, susceptibility to infections. Further, dysregulation or overproduction of nitric oxide has been implicated in the pathogenesis of many disorders, including atherosclerosis, neurodegenerative diseases, inflammatory autoimmune diseases, and cancer. Therefore, depending upon the levels of nitric oxide generated, the potential exists for nitric oxide to behave like a "double-edged" biological sword. Taking these issues into consideration, it is thus pivotal to understand the regulation of nitric oxide. Nitric oxide is regulated by many endogenous factors including hormones such as estrogens. While the effects of estrogen on the generation of nitric oxide in non-immune tissues are relatively well documented, the effect of estrogen on iNOS/nitric oxide in immune cells is only now becoming apparent. Our laboratory has recently shown that estrogen treatment of mice markedly upregulates the levels of iNOS mRNA, iNOS protein, and nitric oxide in activated splenocytes. This upregulation of nitric oxide is in part mediated through interferon-gamma (IFN-gamma), a pro-inflammatory cytokine that is enhanced by estrogen. These findings are important considering that estrogens are not only involved in regulation of normal immune responses, but also are implicated in many autoimmune and inflammatory diseases. To date, there are no reviews on the effects of estrogen on immune tissue-derived nitric oxide and therefore this review will address this critical gap in the literature. Given the increasing importance of immune-tissue-derived iNOS in health and disease, studies on estrogen-induced regulation of iNOS may offer a better understanding of diseases and aid in devising new therapeutic interventions.

Animals↗
PubMed2006

Interferon regulatory factor-1 gene deletion decreases glomerulonephritis in MRL/lpr mice.

To investigate the role of interferon regulatory factor-1 (IRF-1) in the development of lupus nephritis, IRF-1(-/-) genotype mice were bred onto the MRL/lpJfas(lpr) (MRL/lpr) background. We examined kidney mesangial cell function and disease progression. Endpoints evaluated included inflammatory mediators, autoantibody production, immune complex deposition, renal pathology, T cell subset analysis, and duration of survival. Mesangial cells cultured from IRF-1(-/-) mice produced significantly lower levels of nitric oxide and IL-12 but not TNF-alpha when stimulated with LPS + IFN-gamma. IRF-1(-/-) mice showed less aggravated dermatitis compared to the wild-type mice. Anti-double-stranded DNA production and proteinuria were significantly decreased in IRF-1(-/-) mice compared to IRF-1(+/+) mice. IgG and C3 deposition as well as glomerulonephritis were decreased in IRF-1(-/-) mice at 26 wk of age compared to the IRF-1(+/+) mice. Splenic CD4- CD8- CD44+ T cells were decreased while CD4+ CD25+ T cells were increased in the IRF-1(-/-) mice when compared to IRF-1(+/+) mice. Survival rates (ED50) were 22 wk for IRF-1(+/+) mice and 45 wk for IRF-1(-/-) mice. These findings suggest an important role of IRF-1 in mediating renal disease in MRL/lpr mice.

Animals↗
PubMed2006

Impact of different cell isolation techniques on lymphocyte viability and function.

The outcome of immunological assays is markedly influenced by the method of isolation of lymphocytes. It is, therefore, important to comparatively assess various techniques of isolation of lymphocytes, an aspect thus far not thoroughly addressed. In particular, the potential of isolation techniques to influence cell recovery, viability, and function has not yet been evaluated. These studies were designed to determine the effect of different mechanical tissue dissociation methods on the viability and function of lymphocytes. Following spleen and thymus removal, the lymphoid organs were dissociated by one of four different tissue dissociation techniques: metallic screen, sheer force slide, commercial stomacher, or plunger-screen. Cells were then enumerated and a trypan blue exclusion technique and 7-amino-actinomycin D (7-AAD) were both employed to assess viability. Mitogen-induced lymphocyte proliferation was measured using the Alamar Blue assay. Cell viability and lymphocyte surface antigen expression were assessed using flow cytometry. No significant differences in lymphocyte viability, morphology, or surface antigen expression were observed among the different techniques. Likewise, cellular apoptosis and necrosis were comparable across all the techniques. However, mitogen induced splenic T-cell proliferation was higher in cells collected using the metallic screen and plunger-screen isolation methods as compared to the sheer force slide or commercial stomacher procedures. These data suggest that cell recovery, morphology, and viability are not affected by isolation techniques. However, lymphocyte function, as assessed by mitogen induced proliferation, was negatively affected by the sheer force slide or commercial stomacher isolation techniques.

Animals↗
PubMed2005

Estrogen up-regulates inducible nitric oxide synthase, nitric oxide, and cyclooxygenase-2 in splenocytes activated with T cell stimulants: role of interferon-gamma.

Estrogen is implicated in many autoimmune diseases and is a robust immunomodulator. For example, it regulates interferon (IFN)-gamma, a cytokine believed to up-regulate inducible nitric oxide synthase (iNOS). A notable gap in the literature is a lack of information on the regulation of nitric oxide in immune tissues by estrogen. We now show that activation of splenocytes with T cell stimulants [concanavalin-A (Con-A) or anti-CD3 antibodies] results in copious release of nitric oxide in splenocyte cultures from estrogen-treated but not placebo-treated mice. Moreover, even a low dose of T cell stimulants induced nitric oxide in splenocytes from estrogen-treated, but not placebo-treated, mice. Con-A-activated splenocytes from estrogen-treated mice also have up-regulated iNOS mRNA, iNOS protein, and cyclooxygenase-2 (a nitric oxide-regulated downstream proinflammatory protein) when compared with controls. Our studies suggest that the induction of nitric oxide by activated splenocytes from estrogen-treated mice is mediated in part by IFNgamma. First, blocking costimulatory signals mediated through interactions of CD28 and B7 molecules by CTLA-4Ig markedly decreased not only IFNgamma but also nitric oxide. Second, estrogen treatment of IFNgamma-knockout (IFNgamma(-)/(-)) mice did not induce iNOS protein or nitric oxide. Finally, in vitro addition of recombinant IFNgamma to Con-A-activated splenocytes from IFNgamma((-)/(-)) mice induced iNOS protein primarily in estrogen-treated mice. Overall, this is the first report to show that estrogen treatment up-regulates IFNgamma-inducible-iNOS gene expression, iNOS protein, nitric oxide, and cyclooxygenase-2 as an indirect consequence of activation of T cells. These findings may have wide implications to immunity and inflammatory disorders including female-predominant autoimmune diseases.

Animals↗
PubMed2005

Short-term administration of 17-beta estradiol to outbred male CD-1 mice induces changes in the immune system, but not in reproductive organs.

The magnitude of an immune response to many foreign and/or self-antigens is known to be gender-dependent and influenced by sex hormones. While the immune consequences of long-term exposure (3 to 5 months) to natural 17-beta estradiol in an inbred mouse model (e.g., C57BL/6, Balb/c) are relatively well-documented, the immunological effects of shorter-term 17-beta estradiol exposure in an outbred mouse model (CD-1) have not been thoroughly evaluated. The male outbred-CD-1 mouse is considered to be less 17-beta estradiol-responsive (in terms of reproductive changes) compared to the inbred mouse. In the present study, CD-1 male mice were dosed with vehicle, or 17-beta estradiol at 2 or 4 micrg/100 g body weight on alternate days over a 7-day period. The immune changes in the developmental organ (thymus) and mature lymphoid organ (spleen) were determined. Thymic organ weight/body weight ratio and thymocyte cellularity decreased with increasing dose of 17-beta estradiol, reaching significance at the 4 microg dose. Although 17-beta estradiol decreased thymocyte numbers, no differences were noted in the relative percentages of major thymocyte subsets (CD4+CD8-, CD4-CD8+, CD4+CD8+, CD4- CD8-) and no evidence of enhanced apoptosis was found. In contrast to the diminished thymocyte numbers, 17-beta estradiol increased splenic lymphocyte cellularity, especially in mice given 4 microg 17-beta estradiol dose. The functionality of splenocytes from mice exposed to 17-beta estradiol was also altered. Supernatants from Con-A activated splenocytes from 17-beta estradiol-treated mice had increased IFN-gamma and decreased IL-4 levels (p < 0.05 at the 4 microg dose). This increase in IFN-gamma in 17-beta estradiol-treated mice was not due to an increase in the relative percentages of T cells, since they were comparable to relative percentages of T cells from oil-treated control mice. In addition, supernatants from cultured splenocytes (both Con A-activated and unstimulated) also had significantly higher levels of nitric oxide activity, especially at the 4 microg 17-beta estradiol dose. These results indicate that short-term 17-beta estradiol treatment in outbred mice, at relatively modest doses (2-4 microg/100 g body weight), altered both thymocytes and splenocytes. These 17-beta estradiol-induced immune changes are compelling, since in these mice, post-17-beta estradiol exposure did not demonstrate robust changes in the male reproductive system (testicular and seminal vesical weights to body weight ratios).

Animals↗
PubMed2004

Diethylstilbestrol exposure during fetal development affects thymus: studies in fourteen-month-old mice.

In utero exposure to diethylstilbestrol (DES) may have long-term immunological alterations after birth. It is hypothesized that in utero exposure to DES may pre-program the thymus to result in aberrant response to a subsequent adult exposure to an endocrine disrupting chemical. Pregnant mice at 14-days gestation were given either DES (0.25 microg; DESprenatal) or vehicle oil (Oil; Oil(prenatal)). One-year after birth, these mice were given a single dose of DES (DESadult) and thymii of these mice were studied two months later. DESprenatal/DESadult female mice had a significant decrease in thymocyte cellularity compared to female controls (Oil(prenatal)/DESadult). In contrast, male DESprenatal/DESadult mice had increased thymic mass and a trend towards increased thymocyte cellularity. There were no significant differences in the relative percentages of major thymocyte subsets, CD4-CD8-, CD4+CD8+, CD4+CD8-, CD4-CD8+, in either female or male DESprenatal/DESadult mice compared to their sex-matched controls. Nevertheless, thymocytes cultured in media alone showed increased percentage of apoptosis in CD4+CD8+ subset from female DESprenatal/DESadult mice compared to similar cultures from sex-matched controls. Interestingly, the percentage of apoptosis of CD4+CD8+ thymocytes in media-only cultures from DESprenatal/DESadult female mice was comparable to in vitro dexamethasone-exposed cultures from Oil(prenatal)/DESadult female mice. This pattern of increased apoptosis of female CD4+CD8+ subset was not noticed in male DESprenatal/DESadult mice. This implies that prenatal DES exposure in female mice intrinsically alters the degree of apoptosis in CD4+CD8+ thymocyte subset. Together, these data imply that prenatal DES exposure induces long-term thymic changes in a sex-related fashion.

Animals↗
PubMed2003

The immune system of geriatric mice is modulated by estrogenic endocrine disruptors (diethylstilbestrol, alpha-zearalanol, and genistein): effects on interferon-gamma.

The immune system is a potential target for estrogenic endocrine disrupters. To date, there is limited information on whether estrogenic endocrine disruptors modulate the immune system of aged individuals. To address this issue, groups of 74-week-old mice were given nine oral doses of selected estrogenic endocrine disrupters: diethylstilbestrol (DES, 3 microg/100 g bw), alpha-zearalanol (0.5 mg/100 g bw), or genistein (0.15 mg/100 g bw) in corn oil, or corn oil alone, over 2.5 weeks. Both developmental (thymus) and mature (spleen) lymphoid organs were affected, although specific effects varied with the chemical. DES significantly decreased thymocyte numbers. However, relative percentages of thymocyte subsets were not altered. While splenic cellularity and percentages of T and B cells were unchanged, splenocytes from DES-exposed mice had significantly decreased ability to proliferate in response to Concanavalin-A (Con-A). Con-A-activated splenocytes from mice treated with genistein or alpha-zearalanol had decreased levels of interferon-gamma (IFNgamma) protein in their culture supernatants compared to similar cultures from oil-treated mice. RT-PCR analysis of Con-A-activated splenocytes revealed that the expression of IFNgamma gene is altered by DES or genistein treatment. Together, these results suggest that estrogenic endocrine disruptors modulate the immune system of aged mice.

Administration, Oral↗
PubMed2003

Immunologic analysis of blood samples obtained from horses and stored for twenty-four hours.

OBJECTIVE: To determine whether immune function can be accurately assessed in blood samples obtained from horses and refrigerated overnight and whether a nonradioactive lymphocyte proliferation assay can be used to evaluate samples obtained from horses. SAMPLE POPULATION: 224 blood samples from 28 clinically normal adult horses. PROCEDURE: Heparinized blood samples were collected. Each sample was divided into 2 equal aliquots. One aliquot was refrigerated overnight to simulate overnight shipping of blood samples, and the other aliquot was evaluated on the day of blood collection. Lymphocytes were isolated and enumerated by use of a modified single-gradient procedure. Cell viability and function were assessed by use of cytologic examination, flow cytometry, and mitogen-induced proliferation assays. Lymphocyte proliferation in response to T- and B-cell mitogens was measured by use of [3H]-thymidine incorporation and a nonradioactive lymphocyte proliferation assay. RESULTS: Lymphocytes refrigerated for up to 24 hours continued to be acceptable for use in immunologic analysis on the basis that they maintained viability and did not have significant alterations in lymphocyte subsets, except for CD8, when compared with freshly isolated lymphocytes. Furthermore, results for mitogen-induced lymphocyte proliferation assays were also comparable between fresh and refrigerated aliquots. CONDUSIONS AND CLINICAL RELEVANCE: The nonradioactive lymphocyte proliferation assay is a reliable alternative to [3H]-thymidine assay for assessing proliferation of equine lymphocytes. Collectively, our results imply that blood samples refrigerated and shipped ovenight to a laboratory can be used to perform cellular-immune assays; results of those assays would enhance a clinician's diagnostic abilities to monitor the efficacy of treatment.

Animals↗
PubMed2002

Immunomodulation by diethylstilbestrol is dose and gender related: effects on thymocyte apoptosis and mitogen-induced proliferation.

It is believed, but not proven, that the immunomodulatory effects of DES may vary with the dose and/or gender. To address these critical gaps in the literature, diethylstilbestrol (DES) was administered to female and male CD-1 mice as four subcutaneous injections for 1 week at 0, 5, 15, and 30 microg/kg bw doses, and immunological and reproductive effects examined a day after the last injection. Female thymuses were significantly larger than their male counterparts. Short-term administration of DES to female or male mice neither induced thymic atrophy nor altered the relative percentages of thymic subsets. Nevertheless, DES treatment of female or male mice induced a dose-related apoptosis of CD4(+)8(+), CD4(+)8(-) and CD4(-)8(+) subsets as analyzed by 7-amino-actinomycin D (7-AAD). Immature CD4(-)8(-) subset of thymocytes from females was also affected by high dose DES. The pattern of mitogen-induced proliferation of splenic lymphocytes varied with the dose of hormone and the gender. In females, splenic lymphocytes from low dose DES (5 microg/kg bw)-treated mice exhibited an increased proliferative response to Con-A, LPS or PMA/ionomycin compared with controls. Similar cultures from mice treated with higher doses of DES (15 or 30 microg/kg bw) did not manifest an increased proliferative response, but rather showed a trend for suppressed proliferation, especially in response to Con-A. In males, DES had minimal effects with the exception of increased proliferative response to Con-A in splenocytes from medium-dose-DES-treated mice. The changes in mitogen-induced proliferation in DES-treated female mice were not mirrored by similar changes in the relative numbers of CD90(+) or CD45R(+) cells, or in ratios of anti-apoptotic Bcl-2 to apoptotic Bax proteins. Con-A-activated splenocytes from DES-treated mice, particularly from females, had a decreased ability to secrete interferon-gamma compared with controls. Taken together, these findings suggest that short-term exposure to DES has differential immunological effects depending upon the dose of hormone and sex.

Adjuvants, Immunologic↗
PubMed2002

Mice lacking the gene for inducible or endothelial nitric oxide are resistant to sporocyst induced Sarcocystis neurona infections.

Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome in horses from the Americas and is usually caused by infection with the apicomplexan parasite, Sarcocystis neurona. Little is known about the role of immunobiological mediators to this parasite. Nitric oxide (NO) is important in resistance to many intracellular parasites. We, therefore, investigated the role of inducible and endothelial NO in resistance to clinical disease caused by S. neurona in mice. Groups of interferon-gamma gene knockout (IFN-gamma-KO) mice, inducible nitric oxide synthase gene knockout (iNOS-KO) mice, endothelial nitric oxide synthase gene knockout (eNOS-KO) and appropriate genetic background mice (BALB/c or C57BL/6) were orally fed sporocysts or Hanks balanced salt solution. Mice were observed for signs of clinical disease and examined at necropsy. Clinical disease and deaths occurred only in the IFN-gamma-KO mice. Microscopic lesions were seen only in the brains of IFN-gamma-KO mice. Results of this study indicate that iNOS and eNOS are not major mediators of resistance to S. neurona infections. Results of this study suggest that IFN-gamma mediated immunity to S. neurona may be mediated by non-NO-dependent mechanisms.

Animals↗
PubMed2001

Effects of long-term estrogen treatment on IFN-gamma, IL-2 and IL-4 gene expression and protein synthesis in spleen and thymus of normal C57BL/6 mice.

Estrogens have been shown to markedly modulate the immune system. One mechanism by which estrogens could modulate the immune system is by regulating cytokines, an aspect not well-studied thus far. To address this issue, normal C57BL/6 orchiectomized mice were given estrogen and its effects on selected cytokines, interferon-gamma (IFN-gamma), interleukin 2 (IL-2) and IL-4 in lymphocytes from a developmental organ (thymus) and a mature lymphoid organ (spleen) examined. Estrogen significantly increased IFN-gamma and IL-2 mRNA in concanavalin-A (Con-A) activated thymocytes, splenic lymphocytes, and in enriched splenic T cells. Estrogen had no marked effect on IL-4 mRNA. While estrogen increased IFN-gamma mRNA in Con-A activated unseparated splenic lymphocytes and enriched splenic T cells, a numerical increase in IFN-gamma was noticed only in the supernatants of Con-A activated unseparated splenic lymphocytes, but not in enriched splenic T cells. This suggests that for optimal secretion of IFN-gamma in estrogen-treated mice, co-stimulatory signals from antigen presenting cells are needed. Gender differences in IFN-gamma and IL-2 mRNA were also evident. Con-A activated splenic lymphocytes from gonadal-intact, untreated female had a pattern of numerical increase in IFN-gamma mRNA, and IFN-gamma and IL-2 protein levels compared to their male counterparts. Taken together, our data suggests that estrogens regulate the expression of cytokines, which could account in part, for the gender differences in immune capabilities.

Animals↗
PubMed1997

Characterization of estrogen-induced autoantibodies to cardiolipin in non-autoimmune mice.

Antibodies to cardiolipin, in humans, have been associated with a variety of autoimmune disorders including anti-phospholipid syndrome, systemic lupus erythematosus and Sjögren's syndrome. These antibodies have also been demonstrated in autoimmune-prone MRL-Mp-lpr/lpr (MRL/lpr), BXSB-Mp-(+yaa) (BXSB) and (NZW x BXSB)F1 mice. In previous work, we had shown that gonadectomized or intact male and female non-autoimmune C57BL/6 mice, upon treatment with estrogen, express autoantibodies to cardiolipin. In this study, we extend these findings and show that the expression of these antibodies persists for months even after the exposure to exogenous estrogen has been terminated. These antibodies are of IgM and IgG, but not IgA, isotypes, and the predominant IgG subisotype is IgG2b. Estrogen-induced antibodies to cardiolipin only minimally cross-reacted with DNA, actin or ovalbumin. The binding of antibodies to cardiolipin from autoimmune human patients in general has been shown to depend upon the presence of a cofactor, beta2-glycoprotein I. We found that in estrogen-treated C57BL/6 mice, as well as in SLE-prone MRL/lpr and BXSB mice, the binding of anti-cardiolipin antibodies to cardiolipin was not enhanced, but rather reduced, in the presence of human beta2-glycoprotein I. Further, addition of exogenous human beta2-glycoprotein I to purified immunoglobulin fractions containing anti-cardiolipin antibodies reduces, rather than enhances, the binding to cardiolipin. Together, these data show that persistent detectable levels of IgG and IgM autoantibodies specific for cardiolipin can be induced in normal mice by estrogen treatment alone (i.e. without administration of autoantigens). Further, we characterize these antibodies regarding their kinetics, cross-reactivity, isotype distribution and cofactor (beta2-glycoprotein I) requirements.

Animals↗
PubMed1993

Immunologic studies of a horse with lymphosarcoma.

Immunological, clinical, and pathological investigations were conducted on a horse with lymphosarcoma. The immunological status was investigated by measuring the level of antibodies by single radial immunodiffusion test and the ability of lymphocytes to proliferate in response to mitogens. Multiple immunological abnormalities were noted in this horse. They were; (1) decreased IgM, IgG, and IgA levels in the serum despite hyperproteinemia; (2) increased in-vitro spontaneous lymphoproliferation which reflects augmented mitosis; (3) decreased lymphoproliferative response to T cell stimulants (e.g. Concanavalin-A (Con-A)) suggesting impaired T cell activation; (4) presence of immunosuppressive factors in serum as demonstrated by in-vitro lymphocyte culture systems. Clinical pathology findings revealed an unusual monoclonal alpha peak in the serum and morphologically abnormal lymphocytes distributed throughout the body. Serum fractionated by fast protein liquid chromatography (FPLC) revealed that the immunosuppressive factors were found in this abnormal alpha peak. The immunopathological findings in this horse are discussed.

Animals↗
PubMed1989

Estrogen induces normal murine CD5+ B cells to produce autoantibodies.

Females have better humoral immune responses and are more susceptible to autoimmune diseases than males. Normal female mice (C57BL/6J, C3H/HeJ, and NZW) have significantly increased spontaneous autoimmune plaque-forming cells (APFC) to mouse erythrocytes pretreated with bromelain (Br-ME) in spleen, peritoneal exudate cell, and bone marrow compared to their male counterparts. A minor subpopulation of B cells, CD5+ B, is thought to produce this autoantibody. As determined by dual color flow cytometry, increased APFC to Br-ME in females is not due to quantitative increase of CD5+ B cells. Rather, it is due to increased numbers or percentages) of CD5+ B cells producing these autoantibodies, because CD5+ B cells from females produced greater numbers of APFC to Br-ME than equal numbers of cells derived from males. The increased autoantibody production in females can be attributed to the effect of estrogen on the immune response because this hormone markedly augments APFC to Br-ME in intact or orchidectomized males. Male hormone had little effect. Importantly, estrogen did not increase the numbers of B or CD5+ B cells but augmented the ability of B cells to produce this response. This was verified when a T cell-depleted B cell fraction or fluorescence-activated cell sorter purified CD5+ B cells from estrogen-treated mice proved more efficient in the production of APFC to Br-ME. These results suggest that the number of CD5+ B cells committed to produce autoantibodies to Br-ME is increased under the influence of estrogen. This is the first demonstration that estrogen can augment the production of natural autoantibodies in normal mice. The overall augmented humoral immune responses in females and the B cell hyperactivity in female predominant autoimmune diseases appears to be due to estrogen.

Animals↗
PubMed1989

Sex hormones and autoimmune rheumatic disorders.

It has now been recognized that there are complex interactions between the gonadal endocrine and the immune systems. The action of sex hormones on the immune system has important physiological and pathological consequences. The preponderance in women of autoimmune diseases in humans and in experimental animals has a basis in sex hormones. Hypoandrogenic/hyperestrogenic states are thought to contribute to the disease process. This article presents evidence for the action of sex hormones in various experimental animal models of autoimmune diseases and discusses several mechanisms of sex hormone action on the immune system. These mechanisms remain complex and it is to be hoped that the recent advances in immunology, endocrinology, pharmacology, and molecular biology will enable the description and clarification of these mechanisms of action.

Animals↗