Search

In different murine systems, delayed-type hypersensitivity (DTH) swelling responses at 24–48 hr after antigen challenge were preceeded by an early 2-hr swelling response. The 24-hr DTH response is thought to depend on this early (DTH-initiating) hypersensitivity response. In this paper we show that in the syngeneic DBA/2-SL2 routine turnout system only an early 2-hr swelling response can be evoked. This early hypersensitivity response was tumour specific and serotonin dependent. The early hypersensitivity response in contact hypersensitivity has been ascribed to antigen-specific T-cell factors. To test whether similar T-cell factors were involved in the early hypersensitivity response in this syngencic turnout system, we have transferred lymph node, spleen lymphocytes and scram from immunized mice into naive recipients. The serum was fractionated in two fractions, a 50,000–80,000 MW fraction, and a 120,000–190,000 MW fraction. In recipients of lymphocytes, total serum and the 50,000–80,000 MW fraction of the serum, an early hypersensitivity response can be evoked. So, these data suggest the involvement of specific T-cell factors in the development of an early hypersensitivity response against syngeneic tumour cells. Despite the development of an early (DTH initiating) hypersensitivity swelling response these immunized animals cannot develop a classical 24-hr swelling response. This absence of the 24-hr response in the presence of the 2-hr response is discussed in relation to the frequently observed immune suppression in tumour-bearing mice. [ABSTRACT FROM AUTHOR]

Antigen-specific T-helper factor (ThE) bears I-A determinants and is I-A restricted in its action. This I-A restriction may be explained by ThF binding, and hence approximating antigen to its own I-A determinants, thereby facilitating recognition by the T cell (I-A presentation theory), or by a recognition site for I-A on the ThF which approximates the antigen to I-A+ antigen-presenting cells (I-A recognition theory). When ThF is produced in F1 mice there may be a dissociation between the I-A phenotype of the ThF and the I-A restriction of any recognition site for I-A. In practice, ThF is made by spleen cells from (CBA × B10)F1 [(H-2k × H-2d)F1] mice pretreated with cyclophosphamide (100 mg/kg) and immunized with picrylated parental spleen cells intravenously (3 × 107). This procedure produces haplotype-restricted contact sensitivity (corresponding to the parental cells) but the unfractionated F1 ThF does not show haplotype-specific restriction in its action. In fact, the F1 mice produces two species of ThE, each bearing determinants of the I-A molecule of one parental haplotype (k or d). When the two species were separated with monoclonal anti-I-Ak and anti-I-Ad antibodies, the genetic restriction in their action corresponded to the phenotype of the I-A determinants that they carried. In a further experiment, F1 ThE was split into its constituent antigen-binding (Ag+ )and antigen non-binding (Ag-)chains by reduction, and the two species of Ag- chains separated with monoclonal anti-I-A antibodies. After complementation with the Ag+ chain, the two species of Ag- chains showed genetic restriction in their action that corresponded to the phenotype of the I-A determinants that they carried. These findings support the I-A presentation hypothesis that antigen-specific ThE acts by approximating antigen to its own I-A determinants, and hence facilitates recognition by I-A-restricted I cells. [ABSTRACT FROM AUTHOR]

The induction of oral tolerance for DTH responses to ovalbumin is impaired in protein- deprived mice. This may be via the effects of protein malnutrition on short-lived T, cells, but an alternative explanation is that the gut handling of antigen is abnormal. We have attempted to transfer tolerance from protein-deprived and control mice to naive recipients by using spleen cells, collected 7 days after an OVA feed at a time when T, cells should be present, or by using serum, collected 1 hr after feeding, which should contain tolerogenic, ‘gut-processed’ antigen. Suppression of DTH was transferred with 7-day spleen cells and with 1-hr serum from normal, protein-sufficient mice. Mice that received spleen cells from protein-deprived donors were not tolerant, but suppression was readily transferred with serum from deprived mice, indicating that their capacity for intestinal antigen processing was normal. Furthermore, the quantity of absorbed antigen in the serum 1 hr after feeding was similar in both protein-deprived and normal groups. The results obtained are consistent with the hypothesis that short-term protein deprivation depletes a population of short-lived T, cells which control DTH oral tolerance. [ABSTRACT FROM AUTHOR]

We have examined the effects of protein deprivation on the induction of oral tolerance for systemic antibody and DTH responses to the protein antigen ovalbumin (OVA). Mice were fed 4% or 24% protein diets from weaning and given a single feed of OVA 2 weeks later (short- term deprivation) or after 10 weeks (long-term deprivation). Tolerance for serum antibody responses was more profound in protein-deprived animals than in 24% protein-fed control groups. Conversely, tolerance for DTH responses was impaired in protein-deprived mice. This was demonstrated both for short-term deprivation, where nutritional rehabilitation after OVA feeding was necessary to demonstrate this effect on DTH, and for long-term deprivation. Furthermore, the effect of short-term deprivation on tolerance for DTH responses was similar to that observed after cyclophosphamide pretreatment of OVA-fed mice. Protein deprivation has disparate effects on the humoral and cell-mediated limbs of oral tolerance, and our results support the hypothesis that this regime selectively depletes a population of suppressor T cells responsible for the fine control of DTH tolerance. [ABSTRACT FROM AUTHOR]

PPD-reactive T cell clones have been used to analyse the nature of T lymphocytes that are involved in the 'heterogenization' of turnout cells. This is a phenomenon where coupling turnout cells to a strong antigen (in this case PPD) causes an enhanced immune response to tumour-specific antigens to be elicited providing that the host shows T cell immunity to the strong antigen (in this case is BCG positive). Clones of T cells with the Lyt1+ 2- phenotype which were unable to mediate delayed-type hypersensitivity but which provided efficient help to hapten-primed B cells were found to potentiate anti-turnout immunity in BCG-negative syngeneic mice when immunized with Con-A-PPD coupled, X-irradiated MC6A tumour cells. There therefore appears to be a mechanism whereby a helper T cell response to one antigen can provide help for the generation of a T cell response to a linked antigen which is analogous to the well-known phenomenon of help to hapten primed B cells. Furthermore the clones of T cells that help B cells the best are those that give maximal augmentation of T cell immunity. [ABSTRACT FROM AUTHOR]

Male and female spleen cells were compared before and after culture for their cytotoxicity to autologous-embryo fibroblasts. Cultures of male cells developed significantly greater reactivity than cultures of female cells. Moreover, while the cytotoxicity derived from cultures of male cells was totally abolished by treatment of effector cells with a mouse anti-T cells antiserum, such an antiserum had less affect on the effector cells of female mouse cultures. [ABSTRACT FROM AUTHOR]