RESUMEN
High Mphi:T cell ratios suppress the immune response to the retroviral superantigen Mls by IFNgamma-triggered production of the arg- and trp-consuming enzymes iNOS and IDO. Attempts to reverse suppression by treatment with pro-inflammatory cytokines revealed that IL-6 improved the T cell response to Mls and the pro-hematopoietic cyokines IL-3 and GM-CSF increased suppression. GM-CSF treatment increased Mphi expression of CD80, a ligand for the immune suppressive B7H1 and CTLA-4 receptors. These results illustrate potential strategies for reversing the suppression of cell-mediated immunity characteristic of the high Mphi:T cell ratios found in many tumors.
Asunto(s)
Citocinas/biosíntesis , Tolerancia Inmunológica/efectos de los fármacos , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Activación de Linfocitos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Neoplasias/inmunología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Linfocitos T/efectos de los fármacos , Animales , Antígenos CD/genética , Antígenos CD/inmunología , Antígenos CD/metabolismo , Antígeno B7-1/genética , Antígeno B7-1/inmunología , Antígeno B7-1/metabolismo , Antígeno CTLA-4 , Comunicación Celular/efectos de los fármacos , Comunicación Celular/inmunología , Células Cultivadas , Citocinas/genética , Citocinas/inmunología , Citocinas/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Inmunoterapia , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Indolamina-Pirrol 2,3,-Dioxigenasa/inmunología , Interferón gamma/biosíntesis , Interferón gamma/genética , Interferón gamma/metabolismo , Activación de Linfocitos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Ratones Endogámicos BALB C , Ratones SCID , Antígenos Estimulantes de Linfocito Menor/inmunología , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/terapia , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/patología , Escape del TumorRESUMEN
Analysis of the immune system of spiny mice (Acomys cahirinus) has been limited. Originally grouped with Mus, Acomys has recently been placed closer to Meriones (gerbils). This study compared immunity in Acomys, Mus, and Meriones. Lymphocytes from all rodents examined proliferated in response to mitogen and superantigen stimulation. Only Mus T cells responded to anti-CD3 stimulation. Acomys, like Meriones, and Mus that express xid, did not respond to thymus-independent type 2 antigens. Flow cytometric analyses revealed that T cell-specific MAbs did not bind Acomys or Meriones lymphocytes. The B cell-specific anti-CD45R (B220) MAb detected all rodent B cells and revealed the absence of a CD45R(lo) subset in the peritoneal cavity of Acomys and Meriones. Bone marrow from Acomys and Meriones failed to reconstitute B cell function in SCID mice. Thus, in terms of immunity, Acomys appears to be more similar to Meriones than Mus.
Asunto(s)
Antígenos T-Independientes/inmunología , Murinae/inmunología , Linfocitos T/inmunología , Animales , Complejo CD3/inmunología , Citometría de Flujo , Gerbillinae , Inmunofenotipificación , Lipopolisacáridos/inmunología , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Ratones SCID , Mitógenos/inmunología , Mitógenos/farmacología , Superantígenos/inmunología , Linfocitos T/citología , Linfocitos T/efectos de los fármacosRESUMEN
Comparative analyses of the ability of lymphoid tissue to present the minor lymphocyte stimulatory (Mls) superantigen Mls-1a in vitro revealed that all tissues containing mature B cells, except peritoneal cavity (PerC) cells, induced Mls-1a-specific T cell activation. Irradiation and mitomycin C treatment, addition of IL-2 and IL-12, and neutralization of IL-10 and TGF-beta did not restore Mls-1a antigen presentation by PerC cells. Co-culture studies revealed that PerC cells actively suppress the T cell response to Mls-1a. PerC cells from severe-combined immune-defective (SCID) mice also suppressed this response indicating that nonlymphoid cells mediate this effect. These results suggest that in addition to antigen processing and presentation, resident peritoneal cavity cells may temper lymphocyte activation.