RESUMO
H-2 syngeneic H and L (Biozzi) mice provide a model to study Leishmania infections in which polar resistant and susceptible phenotypes are independent from H-2 differences. High-Ab-responder (H) and low-Ab-responder (L) mice syngeneic at the H-2 locus (H-2q) were, respectively, susceptible and highly resistant to Leishmania amazonensis infection. L-mice resistance was associated with high IFN-gamma and transient IL-4 production by lymph node (LN) cells, in contrast with sustained IL-4 and decreasing IFN-gamma production by susceptible H mice. IL-12 production could be detected only in LN from resistant mice. The cytokine production pattern was consistent with preferential progression to a Th1-type response in resistant L-mice, and to a Th2-type response in susceptible H-mice. We also investigated whether this shift towards Th1- or Th2-type cytokine responses was dependent upon H or L antigen presenting cells' (APC) intrinsic ability to preferentially stimulate either T-cell subset. To this end, LN-derived T-cell lines were grown from 12-day infected mice, when both strains produced IFN-gamma and IL-4. L-derived T-cell lines developed a Th2 cytokine pattern whereas H-derived T-cell lines produced IFN-gamma, IL-4 and IL-10 whatever the APC origin (H or L) used for their derivation. This work constitutes the first characterization of cellular immune responses to the intracellular parasite, L. amazonensis in H-2 syngeneic mice, an infection model in which polar resistant and susceptible phenotypes are determined by non-MHC genes.
Assuntos
Células Apresentadoras de Antígenos/imunologia , Citocinas/metabolismo , Antígenos H-2/imunologia , Leishmaniose Mucocutânea/imunologia , Linfócitos T/imunologia , Animais , Linfócitos B/imunologia , Separação Celular , Feminino , Linfonodos/imunologia , Ativação Linfocitária , Masculino , Camundongos , Camundongos EndogâmicosRESUMO
The T-cell compartment was investigated in two high antibody responder lines of mice respectively susceptible (HI) and resistant (HII) to chicken collagen (CII)-induced arthritis (CIA). Previous data had shown that both lines were high anti-CII Ab producers, without any TCR V-beta gene defect or membrane expression impairment. The present studies demonstrate that anti-CII proliferation is much lower in HII than in HI. These results are confirmed by the limiting dilution analysis of anti-CII T-precursor frequencies (1/991 in HI and 1/12175 in HII). The percentage of CD8+ T cells is constitutively higher in HII mice, this difference increasing after CII immunization. This finding suggests a suppressive effect accounting for resistance to CIA. However, no restoration of specific response was achieved by in-vivo or in-vitro depletion of CD8+ T cells. T clones specific for Chicken CII could be obtained only from primed HI mice. Four of five clones with CD8+ phenotype proliferated in vitro to native and denatured CII and showed cytotoxic function in an anti-CD3 redirected assay. The CD4+ clone was shown to proliferate on both HI and HII-pulsed APC, which rules out a major CII processing/presentation defect in HII.
Assuntos
Artrite Experimental/imunologia , Colágeno , Linfócitos T/imunologia , Animais , Formação de Anticorpos/genética , Formação de Anticorpos/imunologia , Artrite Experimental/induzido quimicamente , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Galinhas , Epitopos , Imunidade Inata/imunologia , Imunização , Ativação Linfocitária/imunologia , Camundongos , Fenótipo , RatosRESUMO
1. The isotype distribution of antibody (Ab) responses to Salmonella antigens (Ag) was investigated in high (H) and low (L) Ab responder lines of mice from Selections III and IV carried out for responsiveness to flagellar (f) and somatic (s) Ag, respectively. 2. Primary immunization resulted in higher Ab titers of all isotypes in response to both Ag in H mice from both selections and was confirmed after booster injections. The interline difference (H-L) in response to the distinct isotypes ranged from 3.0 to 7.0 log2 to Ag f in Selection III and from 2.0 to 5.1 log2 to Ag s in Selection IV. 3. Comparison of isotype production to 3 Ag in Selections I, II, III and IV demonstrated that: 1) the highest responses in all mice are those against the selection Ag, 2) the isotypic pattern depends on both the Ag injected and the host's genetic constitution, and 3) the presence or lack of a multispecific effect is not due to isotype-restricted regulation.
Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Isotipos de Imunoglobulinas/análise , Salmonella typhimurium/imunologia , Animais , Reações Antígeno-Anticorpo , Ensaio de Atividade Hemolítica de Complemento , Ensaio de Imunoadsorção Enzimática , Imunização Secundária , Isotipos de Imunoglobulinas/biossíntese , Isotipos de Imunoglobulinas/imunologia , CamundongosRESUMO
The isotype distribution of antibody (Ab) responses to Salmonella antigens (Ag) was investigated in high (H) and low (L) Ab responder lines of mice from Selections III and carried out for responsiveness to flagellar (f) and somatic (s) Ag, respectively. Primary immuniztion resulted in higher Ab titers of all isotypes in response to both Ag in H mice fro m both selections and was confirmed after booster injections. The interline difference (H-L) in response to the distinct isotypes ranged from 3.0 to 7.0 log2 to Ag f in Selection III and from 2.0 to 5.1 log2 to Ag s in Selection IV. Comparison of isotype production to 3 Ag in Selections I,II,III and IV demonstrated that: 1) the highest responses in all mice are those against the selection Ag, 2) the isotypic pattern depends on both the Ag injected and the host's genetic constitution, and 3) the presence or lack of a multispecific effect is not due to isotype-restricted regulation
Assuntos
Animais , Antígenos de Bactérias/análise , Genes MHC da Classe II , Isotipos de Imunoglobulinas/análise , Salmonella typhimurium/imunologia , Reações Antígeno-Anticorpo , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Ensaio de Atividade Hemolítica de Complemento , Ensaio de Imunoadsorção Enzimática , Imunização Secundária , Isotipos de Imunoglobulinas/biossíntese , Isotipos de Imunoglobulinas/genética , Isotipos de Imunoglobulinas/imunologia , Camundongos/sangueRESUMO
Susceptibility to Salmonella typhimurium infection was compared in H (high Ab responder) and L (low Ab responder) mice obtained by several selective breeding experiments (Selections I, II, III, IV and IV A). H mice were always much more susceptible to infection than their L mice counterparts within a continuous LD 50 variation range. In three of the selections (I, II and IV A) the low responsiveness character is known to result mainly from rapid Ag degradation in L mice macrophages. It was hypothesized that resistance to multiplication of intracellular pathogens could be related to an increased catabolic activity towards Ag. This was actually demonstrated, in F2 segregant hybrids of selection IV A, by the significant inverse correlation between capacity for Ab production and resistance to infection.
Assuntos
Anticorpos Antibacterianos/análise , Salmonelose Animal/imunologia , Animais , Feminino , Imunidade Celular , Lipopolissacarídeos/toxicidade , Macrófagos/fisiologia , Masculino , Camundongos , Salmonella typhimurium/imunologia , Ovinos , Choque Séptico/imunologiaRESUMO
The high (H) and low (L) antibody responder lines of mice produced by selective breeding are characterized by different modifications in immunocompetent cell potentialities, according to the immunization procedure used for the selection process. In selections I and II, the difference in antibody responsiveness between H and L lines was clearly shown to depend mainly on macrophage function: the more rapid catabolism of antigens in L mice was the main cause of the low antibody production. In contrast, up to now, no difference has been observed between H and L mice of selections III and IV in terms of the macrophage accessory role. The administration of silica particles has a well known impairment effect on macrophage activity. Therefore, the effect of silica injection on the kinetics of antibody responses to selection antigens was compared in H and L mice of the four selections. Silica was given either intravenously or locally in one hind footpad 6 or 24 h before immunization by the same route. Silica treatment consistently improved antibody responsiveness in the L mice of selections I and II, but had no effect in the L mice of selections III and IV. The antibody responses of the H lines of the four selections were not substantially modified by silica injections. Therefore, the silica treatment reduced the interline difference in antibody responses in selections I and II only, by interfering with the expression of the genetic modification of macrophage activity. However, a similar effect was not obtained with other substances known to affect macrophages, including dextran sulphate or carrageenan. The results reported here are in agreement with the above-mentioned statement that the genetic modification of macrophage function plays a major role in the interline difference in selections I and II and is not involved in selections III and IV.