In vivo cyclophosphamide-mediated augmentation and aqueous HGG-induced suppression of murine delayed hypersensitivity to HGG are reflected by in vitro HGG-stimulated proliferation of lymph node cells from equivalent mice

Clark, Connie; Wheelock, Margaret J.

doi:10.1016/0008-8749(80)90361-5

Cited by 7 publications

(1 citation statement)

References 22 publications

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“…Another possibility to explain a normal or exacerbated DTH, was that treatment with CY before immunization produces a depletion of precursor cells involved in the suppression of DTH. [16][17][18][19] There is not considerable evidence in support of the suppressive action of CY on DTH when the drug is used after the immunization. In contrast with our finding Kerckhaert et al 20 have shown an enhancing of DTH when the drug is injected prior or after intracutaneous immunization of sheep red blood cells (SRBC) in CFA.…”

Section: Discussionmentioning

confidence: 99%

Specific Suppression of Humoral and Delayed Hypersensitivity Responses by Cyclophosphamide in an Experimental Model of Autoimmunity

Riera

Galmarini

Serra

1983

American Journal of Reproductive Immunology

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The aim of this report is to investigate the effect of cyclophosphamide (CY) in an experimental model of autoimmunity to rat male accessory glands. The results indicated that 100 mg/kg of this drug suppressed humoral immune response that persisted for at least 45 days when administered 3 days after the first immunization of rats with modified rat male accessory glands (MRAG) in complete Freund's adjuvant (CFA). Administration of the drug 3 days before ID injection of antigen caused a shorter suppression of antibody formation. Delayed type hypersensitivity (DTH) studied 13 days after the first immunization was suppressed only in the animals that were administered CY after the antigen. The specificity of the immunosuppression was studied in rats treated with CY after the first immunization with MRAG using aggregated human gamma-globulin (AHGG) as an unrelated antigen. The studies demonstrated significant suppression of DTH (p less than 0.005) and humoral immunity only against MRAG. On the contrary, the response to AHGG was not significantly modified.

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Section: Discussionmentioning

confidence: 99%

Specific Suppression of Humoral and Delayed Hypersensitivity Responses by Cyclophosphamide in an Experimental Model of Autoimmunity

Riera

Galmarini

Serra

1983

American Journal of Reproductive Immunology

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Evidence That X-Irradiation and 4-Hydroperoxycyclophosphamide Affects Different Lymphocytes That Respond to Specific Antigen In Vitro

Clark

LaSota

Borch

1985

Journal of Leukocyte Biology

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The present study examined the effect of pulse treatment with the in vitro active synthetic derivative of cyclophosphamide (CY), 4-hydroperoxycyclophosphamide (4-HPCY), and exposure to X-irradiation on the in vitro Concanavalin A (ConA), lipopolysaccharide (LPS), and antigen-specific blastogenic responses of in vivo-primed lymph node cells. Primed lymph node cells from CY-pretreated, aggregated (A) human IgG-complete Freund's adjuvant (AHGG-CFA)-immunized mice were untreated, exposed to various doses of irradiation, or pulse treated with different concentrations of 4-HPCY before being cultured in medium alone or in medium containing HGG, ConA, or LPS. The results show that HGG-responding and LPS-responding cells exhibited similar dose-inactivation profiles following exposure to irradiation or pulse treatment with 4-HPCY. More than 75% of reactivity was eliminated by exposure to 100 rads or pulse treatment with 20 microM 4-HPCY. In contrast to preculture pulse treatment with 4-HPCY, however, when primed lymph node cells were cultured in medium containing 4-HPCY (culture treatment) LPS-responding cells were shown to be more sensitive to inactivation than HGG-responding cells. The data further show that the effect of low-dose irradiation and of culture treatment with 4-HPCY on the HGG-specific response of primed lymph node cells was additive, suggesting that these agents inactivate different cell subtypes that contribute to the HGG-specific response in vitro.

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Low-Dose X-Irradiation and 4-Hydroperoxycyclophosphamide Distinguishes Three LYT-1+ Lymph Node T-Cell Subtypes That Respond to Specific Antigen In Vitro

Clark

LaSota

Borch

1987

Journal of Leukocyte Biology

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We investigated whether preculture exposure to low-dose X-irradiation and culture treatment with 4-hydroperoxycyclophosphamide (4-HPCY), a synthetic derivative of cyclophosphamide (CY), might distinguish subtypes of thymic-dependent (T) lymphocytes that respond to specific antigen in vitro. Lymph node (LN) cells were obtained from mice pretreated with CY and immunized with aggregated (A) human IgG (HGG) in Freund's complete adjuvant (CFA), and proliferation was assessed by incorporation of tritiated thymidine. Primed LN cells were untreated or exposed to low-dose irradiation before being cultured in medium alone and in medium containing 4-HPCY. The results show that these agents (irradiation and 4-HPCY) distinguished, in a dose-dependent manner, subtypes of T-cells which contribute to the specific antigen-stimulated proliferative response in vitro. For LN T-cells and LN Lyt-1+ T-cells, 20-25 rads and 1.0 microM 4-HPCY inactivated non-overlapping cell subtypes that respectively accounted for 26% and 28% of the response to HGG. The remaining 46% of HGG-responding cells were not affected by either agent. Although similar cell subtypes were discerned in unseparated LN cells, it required use of higher agent-doses. Cell cycle analysis revealed that treatment with irradiation, 4-HPCY, and the combination (both agents) caused S-phase arrest of 29%, 30%, and 55% of HGG-responding cells, respectively. Thus, identification of these cell subtypes could not be attributed to agent-mediated inactivation of HGG-responding cells that might be in exclusively different phases of the cell cycle.

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In vivo cyclophosphamide-mediated augmentation and aqueous HGG-induced suppression of murine delayed hypersensitivity to HGG are reflected by in vitro HGG-stimulated proliferation of lymph node cells from equivalent mice

Cited by 7 publications

References 22 publications

Specific Suppression of Humoral and Delayed Hypersensitivity Responses by Cyclophosphamide in an Experimental Model of Autoimmunity

Specific Suppression of Humoral and Delayed Hypersensitivity Responses by Cyclophosphamide in an Experimental Model of Autoimmunity

Evidence That X-Irradiation and 4-Hydroperoxycyclophosphamide Affects Different Lymphocytes That Respond to Specific Antigen In Vitro

Low-Dose X-Irradiation and 4-Hydroperoxycyclophosphamide Distinguishes Three LYT-1+ Lymph Node T-Cell Subtypes That Respond to Specific Antigen In Vitro

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