Disproportion in T-cell subpopulations in immunodeficient mutant hr/hr mice.

Reske‐Kunz, Angelika B.; Scheid, M P; Boyse, Edward A.

doi:10.1084/jem.149.1.228

Cited by 32 publications

(11 citation statements)

References 10 publications

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“…A slightly depressed Thy1.2 expression was evident only the day after the last DES treatment. Irrespective of neonatal treatment the cytotoxicity index (CI; Thy1.2 antibodies) in splenocyte suspensions from 12-wk-old and 1-yr-old females was higher than in suspensions from 8-wk-old females, which is in line with an earlier described age-related increase in the spleen Thy1+ cell population (Reske-Kunz et al, 1979;Kalland, 1980). In old mice (40 wk) the spleen Thy1+ population was found to be decreased (Yoshikai et al, 1988), which is contrary to our findings of a stable level of Thy1.2-related CI in spleens from 12-wk-old and 1-yr-old females.…”

Section: Discussionsupporting

confidence: 76%

Neonatal Estrogen Treatment and Its Consequences for Thymus Development, Serum Level of Autoantibodies to Cardiolipin, and the Delayed-Type Hypersensitivity Response

Forsberg

2000

Journal of Toxicology and Environmental Health, Part A

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Eight-week-old female and male NMRI mice treated neonatally with the synthetic estrogen diethylstilbestrol (DES), estradiol-17beta, or tamoxifen displayed an enlarged thymus when compared with controls (approximately 1.5-fold). In control females, either ovariectomy or adrenalectomy increased thymus weight to the level characteristic for DES-treated females, but these endocrine ablations had no significant effect in DES females. The serum estrogen levels were similar in intact DES, ovariectomized DES, and ovariectomized female controls; serum corticosterone was similar in controls and DES females. The expression of the Thy1.2+ marker and the percentages of CD4+CD8+ DP and CD4+ and CD8+ SP cell subsets were similar in thymocyte populations from 8-wk-old controls and DES females; the CD4+ and CD8+ SP subsets were similar in splenocyte populations. The levels of serum immunoglobulin (Ig) G and IgM autoantibodies to cardiolipin showed age-dependent fluctuations but were similar in controls and DES females; however, the IgG autoantibodies in DES females were qualitatively different from those in controls with respect to sensitivity to bovine serum (a source of beta2-glycoprotein I). Contrary to females, DES-treated males had higher levels of autoantibodies than controls. The delayed-type hypersensitivity (DTH) response to oxazolone was similar in controls and DES animals at 8 wk, increased in DES females and males at 6 mo, but was reduced in DES females at 1 yr. Thus, even though adult mice with thymus enlargement after neonatal estrogen treatment do not differ from controls with respect to the expression of the Thy1.2 marker or percentages of CD4+/CD8+ DP or SP subsets in thymus and spleen, qualitative and quantitative differences occur in immune parameters (autoantibodies to cardiolipin) and a T-cell-dependent immune response (DTH).

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Section: Discussionsupporting

confidence: 76%

Neonatal Estrogen Treatment and Its Consequences for Thymus Development, Serum Level of Autoantibodies to Cardiolipin, and the Delayed-Type Hypersensitivity Response

Forsberg

2000

Journal of Toxicology and Environmental Health, Part A

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“…In Leishmania- Furthermore Hairless mice exhibit a mild immunodeficiency, associated with abnormalities in T-cells (Morrisey et al, 1980;Rezke-Kunz et al, 1979). Zarach et al (2004) showed that the Hr gene encodes a protein highly expressed in skin and brain, which acts as a transcriptional co-repressor for some nuclear receptors such as thyroid hormone, retinoic acid, and vitamin D receptors.…”

Section: Accepted Manuscriptmentioning

confidence: 96%

Hairless mice as an experimental model of infection with Leishmania (Leishmania) amazonensis

Araujo

Fukutani

Oshiro

et al. 2015

Experimental Parasitology

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HRS/J Hairless mice have been investigated as an experimental model in cutaneous leishmaniasis induced by Leishmania (Leishmania) amazonensis. The animals were inoculated with 10(6) promastigotes into the right hind footpad and the course of infection was followed up for 30, 60 and 90 days. BALB/c mice were infected and used as control. Hairless mice were susceptible to L. (L.) amazonensis infection and a progressive increase in number of parasites and footpad thickness was detected over time. Signals of dissemination and visceralization were confirmed by the presence of parasite in the draining lymph node of lesion and spleen, at different times post infection. IL-10 gene expression evaluated by RT-PCR was significantly higher in Hairless mice at 60 days post infection, corroborating the pattern of susceptibility. These results point this inbred strain as a promising susceptible model for the study of experimental infection induced by L. (L.) amazonensis. This model would allow the use of other infection sites that minimize secondary interference and best monitoring the skin lesion, as in the case of in vivo assays of potential drugs for LT.

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“…Animals with this genotype also possess a quantitative deficiency of T lymphocytes; specifically, the ratio between Ly1 and Ly123 lymphocytes is reversed in the spleens of 3-to 3.5-month-old mice, without affecting the total lymphocytes counts (31). These animals have a defect in the proliferative response to alloantigens but no defect in mitogenic responses or lymphocyte cytotoxicity (25).…”

Section: Discussionmentioning

confidence: 99%

Contribution of CsrR-Regulated Virulence Factors to the Progress and Outcome of Murine Skin Infections byStreptococcus pyogenes

Engleberg

Heath²,

Vardaman³

et al. 2004

Infect Immun

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Streptococcus pyogenes with null mutations in the csrRS regulatory locus are highly virulent in mice due to derepression of hyaluronic acid capsule synthesis and exotoxins, e.g., streptolysin S (SLS) and pyrogenic exotoxin B (SpeB). We generated derivatives of a ⌬csrRS strain that also carry deletions in hasAB (leading to an acapsular phenotype) or in sagA (phenotypically SLS ؊ ) or an interruption of speB (SpeB ؊ ) to test the relative contributions of these factors to the development of necrotic skin lesions. Inoculation of 2 ؋ 10 6 to 4 ؋ 10 6 CFU of either acapsular or SLS ؊ strains into hairless mice resulted in lesions ϳ70% smaller than those of the ⌬csrRS parent strain. Elimination of SLS also reduced lethality from 100% to 0% at this inoculum (P < 10 ؊7 ; Fisher exact test). In contrast, SLS ؉ SpeB ؊ mutants yielded lesions that were only 41% smaller than the parent strain (t ‫؍‬ 2.2; P ‫؍‬ 0.04), but only 3 the 17 lesions had dermal sloughing (P ‫؍‬ 10 ؊5 ). The nonulcerative lesions associated with SpeB ؊ strains appeared pale with surrounding erythema. We conclude that capsule and SLS contribute to the subcutaneous spread of S. pyogenes and to a fatal outcome of infection. SpeB facilitates early dermal ulceration but has minor influence on lesion size and mortality. Large ulcerative lesions are observed only when both toxins are present.Enhanced virulence of Streptococcus pyogenes csrR mutants is associated with increased expression of the hyaluronic acid capsule and several exotoxins, most notably streptolysin S (SLS) and pyrogenic exotoxin B (SpeB, or cysteine proteinase) (12). In the hairless mouse model of streptococcal skin infection, csrR mutants produce rapidly expanding, necrotic lesions, whereas the CsrR ϩ wild-type M1 strain from which they are derived induces only small abscesses or self-limited erythema.There is little disagreement about the importance of the hyaluronic acid capsule in streptococcal pathogenesis; however, significant controversy exists concerning the importance of many of the other CsrRS-regulated gene products in virulence. Several research groups have characterized SLS as a key factor contributing to virulence (4,17,28). In contrast, discrepancies have been reported concerning the importance of cysteine proteinase in studies with speB mutants (2,3,21,24,32,34). We hypothesized that the incremental pathogenicity associated with the mutations in csrR depends on the expression of these regulated virulence factors. Accordingly, we characterized here the impact of these toxins on murine infection by deleting them individually or in combination in S. pyogenes strains lacking CsrR. We show an additive effect of hyaluronic acid capsule, SLS, and SpeB on mouse virulence, and we observe that these factors contribute in different ways to the character, extent, and lethality of the skin lesions. MATERIALS AND METHODSAll experiments used derivatives of a type M1 isolate, MGAS166 (27). Streptococci were stored at Ϫ70°C and passaged minimally before and after genetic manipulations. Tod...

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Disproportion in T-cell subpopulations in immunodeficient mutant hr/hr mice.

Cited by 32 publications

References 10 publications

Neonatal Estrogen Treatment and Its Consequences for Thymus Development, Serum Level of Autoantibodies to Cardiolipin, and the Delayed-Type Hypersensitivity Response

Neonatal Estrogen Treatment and Its Consequences for Thymus Development, Serum Level of Autoantibodies to Cardiolipin, and the Delayed-Type Hypersensitivity Response

Hairless mice as an experimental model of infection with Leishmania (Leishmania) amazonensis

Contribution of CsrR-Regulated Virulence Factors to the Progress and Outcome of Murine Skin Infections byStreptococcus pyogenes

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