Development Of Delayed-type Hypersensitivity Research Articles

Effect of allogeneic challenge dose and cyclophosphamide treatment on the development of delayed-type hypersensitivity and cell-mediated cytotoxicity.

Mice were challenged with high (10(8)) or low (10(4)) numbers of allogenic tumor cells and assessed for cellular immunity. The responses obtained indicated that high dose challenge produced both delayed-type hypersensitivity (DTH) and cell-mediated cytotoxic reactivity (DCMC), while low dose challenge produced DTH, an apparent suppressive effect, and little or no DCMC. Pretreatment with 100 mg/kg of cyclophosphamide (CTX) 3 d before antigen failed to alter this pattern, but treatment 3 d after antigen administration abrogated both DTH and DCMC. Animals given a combined modulating protocol consisting of an initial low dose challenge followed on day 3 by CTX treatment and day 6 by a high dose challenge developed DCMC in the presence of a greatly reduced or absent DTH response. These results demonstrate the differential effects of allogeneic challenge dose on the development of cellular immunity; the differential effects of CTX treatment given prior to or following alloimmunization, and demonstrate how these effects can be combined to modulate the immune response by selectively activating subpopulations of T-lymphocytes.

Relationship between delayed-type hypersensitivity and the progression of Mycobacterium lepraemurium infection

The relationship between the level of delayed-type hypersensitivity (DTH) and the progression of Mycobacterium lepraemurium infection was examined after inoculation of mice with 10(8) M. lepraemurium in the left hind footpad. The expression of DTH developed over the first 4 weeks of infection, remained high up to week 8, and then dropped to a low level at which it remained for 12 more weeks. The development of DTH was concordant with an initial swelling of the inoculated foot, the appearance of a mononuclear infiltrate at this site, and a prevention of any increase in the number of mycobacteria in this foot and in other tissues studied. A decay of DTH reactivity was associated with a progressive increase in the number of M. lepraemurium initially at the original site of inoculation and subsequently in all other tissues. Although the expression of DTH was lost, adoptive immunization experiments showed that a population of sensitized lymphocytes persisted within host. Further experimentation offered evidence to suggest that the level of systemic antigen may be in part responsible for the loss of DTH reactivity.

Changes in host resistance caused by Nocardia brasiliensis in mice: cross-protection against Listeria monocytogenes.

Listeria monocytogenes was used to study the rate of development, magnitude, and persistence of the antimicrobial resistance engendered by Nocardia brasiliensis infection in mice. The growth of Listeria in the liver and spleen was more effectively restricted in Nocardia-infected mice than in noninfected animals. The development of delayed-type hypersensitivity to the Nocardia antigen was closely correlated to the increased resistance to Listeria, suggesting that both properties are the consequence of a single immunological event. The antibacterial resistance was also demonstrated in vitro. The results of the foregoing studies indicate that the microbicidal ability of macrophages, very likely activated by cell-mediated immunity, in enhanced in mice infected with Nocardia.

Development of delayed-type hypersensitivity during Mycobacterium lepraemurium infection in mice

Various preparations of Mycobacterium lepraemurium were used to elicit delayed-type hypersensitivity in the footpad of mice infected with this organism. With a sonicated preparation of the mycobacterium, a significant increase in footpad swelling was elicited in mice infected with M. lepraemurium 5 weeks previously, but not in BCG-infected animals or uninfected controls. This footpad reaction was shown to peak at 24 h and to be associated with an infiltration of mononuclear cells. The kinetics of footpad swelling, its association with lymphoproliferation, and its dependence on T lymphocytes were each examined. The results support the hypothesis that this is a delayed-type hypersensitivity reaction. The ability to transfer this reactivity to normal mice with cells but not serum offers further confirmation that this hypersensitivity is dependent on cell-mediated immunological mechanisms rather than humoral antibody. The relevance of this to the study of the immunological response of mice to murine leprosy is discussed.

Influence of dose and route of antigen injection on the immunological induction of T cells.

Delayed-type hypersensitivity (DTH) develops in the absence of an adjuvant when mice are injected intravenously or subcutaneously with an appropriate dose of sheep red blood cells (SRBC). The optimal intravenous dose of 10(5) SRBC (in CD-1 mice) produces maximum DTH which decays exponentially from its peak on day 4. Increasing the dose of SRBC reduces and eventually abolishes all evidence of DTH. DTH fails to reappear in respose to secondary stimulation except in splenectomized mice in whom the development of DTH is not suppressed, even by massive doses of SRBC. Hence the suppression cannot be due to antigen as such. The optimal dose of SRBC for sensitization by footpad inoculation is 100-fold higher (10(7) SRBC in CD-1 mice), but even 10(9) SRBC do not block the induction of DTH by this route of immunization. A blocking dose of SRBC, given intravenously 1 day before footpad inoculation, completely suppresses cell proliferation in the draining lymph node, prevents PFC production there, and blocks the induction of DTH by a sensitizing dose of SRBC. If given 1 day after footpad sensitization, intravenous antigen has little effect on the cellular response in the regional node but DTH is still completely suppressed. Blocking of induction and expression may depend, therefore, on different mechanisms.

In Vivo and In Vitro Studies of Delayed-Type Hypersensitivity to Toxoplasma gondii in Guinea Pigs

Delayed-type hypersensitivity develops late in the course of human toxoplasmosis, and a positive skin test is of some value for implicating chronic or eliminating acute forms of toxoplasmosis as a cause of disease. Toxoplasma-infected guinea pigs were studied to determine the onset and development of delayed-type hypersensitivity. Both the toxoplasmin skin test and the in vitro macrophage migration inhibition technique indicated that delayed hypersensitivity to toxoplasma antigen existed as early as 1 week after infection. The mechanism responsible for the observed inhibition of macrophage migration in vitro appeared to be an inhibitory factor(s) released from sensitized lymphoid cells in the presence of antigen.

Development of delayed-type hypersensitivity in guinea pig embryos.

SEVERAL, modalities of the immune response of embryos have been previously investigated. These include : (a) induction of immunological tolerance1; (b) antibody formation2; (c) capacity to reject homografts3. There have been no analogous studies of the capacity of the embryo to develop the delayed type of hypersensitivity to protein antigens.