In vivo immune responses to Candida albicans modified by treatment with recombinant murine gamma interferon.

The immunologic effects of in vivo administration of recombinant murine gamma interferon (rMuIFN-gamma) were determined in a murine model of candidiasis. Naive mice were given graded doses of rMuIFN-gamma and then challenged intravenously with Candida albicans. Increased morbidity and mortality were noted in four different strains of mice, viz., BALB/c, A/J, Swiss Webster, and CBA/J, providing the mice had not been immunized with C. albicans before challenge. Quantitative culture of selected organs of Swiss Webster and CBA/J mice surviving treatment with rMuIFN-gamma revealed elevated numbers of C. albicans cells, particularly in the kidneys, but also in the liver, lungs, and spleen. The lungs, livers, and spleen of female CBA/J mice were more protected from increased multiplication of the fungus than were those of males of the same species or female Swiss Webster mice. On the basis of these initial findings, the effect of treatment with 5,000 U of rMuIFN-gamma on immune responses in a gastrointestinal model of candidiasis was determined. CBA/J mice that had been colonized with C. albicans as infants were boosted with a cutaneous inoculation of the fungus when 6 to 10 weeks old; development of delayed hypersensitivity (DH), antibodies, and protective responses was assayed at intervals thereafter. Daily treatment with rMuIFN-gamma (beginning 1 day before cutaneous inoculation) suppressed weak immune responses but had little effect on responses which were strong. For example, DH and anti-C. albicans antibody production were suppressed in animals colonized with C. albicans but not boosted by cutaneous inoculation, and DH was suppressed in uncolonized animals that had been inoculated once cutaneously with the fungus as well. There was no rMuIFN-gamma-induced suppressive effect of DH in mice which had been stimulated maximally with C. albicans, i.e., colonized animals that had been boosted cutaneously with the organisms. Collectively, these data indicate that naive mice or mice with minimal levels of anti-C. albicans sensitivity, females somewhat more so than males, were sensitive to suppressive effects of in vivo treatment with rMuIFN-gamma when challenged with C. albicans. In contrast, under conditions similar to those of humans, in whom underlying immunity to C. albicans is usually present, suppression of host responses to C. albicans was not observed in immunized mice in response to treatment with rMuIFN-gamma.     

Nonspecific and Candida-specific immune responses in mice suppressed by chronic administration of anti-mu

CBA/J mice were immunosuppressed by repeated administration of goat antibody specific for mu chain of immunoglobulin M (IgM) and tested for nonspecific and Candida albicans-specific immune responses. Immunosuppression was demonstrated by a dramatic reduction in the number of antibody-forming cells in the spleens of anti-mu-treated mice when immunized with sheep erythrocytes, by greatly reduced in vitro responsiveness of both spleen and lymph node lymphocytes from anti-mu-treated mice to lipopolysaccharide, and by a large reduction in the number of splenic IgM-positive cells. T cell function, on the other hand, appeared to be relatively unaltered in anti-mu-treated animals, in the cytotoxic T lymphocyte activity against an allogeneic target was similar in splenocyte cultures from anti-mu- and mock-treated animals, and splenic and lymph node lymphocytes proliferated in response to concanavalin A in a lymphocyte stimulation assay. Moreover, Candida-specific delayed hypersensitivity to two different Candida antigens, one cell wall-derived (GP) and the other cell membrane-derived (BEX), was of comparable intensity in immunosuppressed and normal animals. When anti-mu- and mock-treated mice were immunized by the cutaneous inoculation of viable C. albicans blastospores and then challenged intravenously to assess the development of protective immunity, only mock-treated animals, male and female, had significant (p less than or equal to 0.05) protective responses demonstrable by reduction in the number of colony-forming units cultured from their kidneys 28 days after intravenous challenge. If consideration was given to the number of animals which had cleared Candida completely from the kidney, however, there appeared to be protective responses operative in the female anti-mu-treated animals as well. Neither anti-mu-treated males nor females, when immunized and challenged with C. albicans, produced Candida-specific antibody detectable by counterimmunoelectrophoresis, whereas all immunized and challenged mock-treated animals produced antibody. The data are consistent with the hypothesis that anti-mu treatment has little effect on multiple cellular immune functions, including those specific for C. albicans, and the combination of antibody, cell-mediated immunity and innate defenses are responsible for solid systemic defense against the fungus.     

Immunodepression in trypanosome-infected mice. VI. Comparison of immune responses of different lymphoid organs

Mitogen stimulation of cells from various lymphoid organs of C3H/He mice chronically infected with an isolate of Trypanosoma congolense was studied at different time intervals after infection, using concanavalin A (Con A) and lipopolysaccharide (LPS). At the same time, changes in the percentages of T, B and null lymphocytes in these organs were determined by immunofluorescence staining. The responses of T and B lymphocytes in the spleen were totally depressed, and the cellular composition was drastically altered by day 14 after infection. Unlike the spleen, the lymph nodes showed minor changes in their T and B lymphocyte responses and cell composition during the course of the infection, except the B cell response and composition which were altered late in the infection. The thymus and bone marrow did not show any appreciable changes in their mitogen responses and cell composition throughout the infection. The peripheral blood lymphocytes showed reduced B cell responses. Spleen cells from chronically infected mice suppressed lymphocyte stimulation induced in normal spleen and lymph node cell populations by Con A, LPS and allogeneic stimulator cells. Lymph node cells from the same group of mice did not exhibit any such suppressor activity. In the experimental system used here, the spleen is the primary site of immune depression, and other lymphoid organs such as the lymph nodes and thymus are very little affected.     

Expression of the C3d-binding protein (CR2) from Candida albicans during experimental candidiasis as measured by lymphoblastogenesis.

The complement C3d-binding protein (CR2) of Candida albicans has been purified by immunoaffinity chromatography, and its specificity has been characterized by immunoblotting with monoclonal antibodies to the C. albicans CR2 and the mammalian CR2. Recent studies with immunoelectron microscopy indicated that the CR2 was expressed during a systemic infection in a murine model of candidiasis. As a continuation of these observations, the immunogenicity of the C. albicans CR2 was investigated in a lymphoblastogenesis assay. Lymph node cells as well as splenic lymphocytes from mice infected subcutaneously with viable blastoconidia of C. albicans reacted to the C. albicans CR2 to a significantly greater extent than did lymphocytes from uninfected mice (P less than 0.01). The maximum stimulation of splenic lymphocytes by the purified receptor occurred at a concentration of 0.54 micrograms of protein per ml after 72 h of incubation of lymphocytes and receptor. Also, splenocytes from infected or CR2-immunized mice exhibited significantly reduced responses to the T-cell-dependent mitogen phytohemagglutinin (P less than 0.01). These data indicate that lymphocytes from infected mice respond to the C. albicans CR2 in a lymphoproliferation assay to a greater extent than do lymphocytes from uninfected mice, indicating that the CR2 is expressed in vivo.     

Age-related changes in responsiveness of various rat tissue lymphocytes to mitogens

The effect of age on the mitogen responses of rat lymphoid tissues was investigated. Evaluation was based on using the in vitro proliferative response of lymphocytes from various tissues of Fischer-344 rats (2, 7, 13, 19 and 25 months) using concanavalin A (Con A), phytohemagglutinin-P (PHA-P), pokeweed mitogen (PWM) and Mycoplasma neurolyticum. The stimulation index (S. I.) for cervical, mesenteric, thymic and splenic lymphocytes treated with Con A and PHA-P was greatest for 2-month-old rats and lowest for 19-month-old rats; however, no age-related change was observed with either PWM or M. neurolyticum. The levels of mitogenic responses for lymph nodes in the two different anatomical sites paralleled one another, with the cervical lymphocytes showing a greater response. The splenic lymphocytes responded less than either lymph node lymphocyte population. When PHA-P treatment of splenic lymphocytes followed the removal of the plastic adherent population, the S. I. of the resulting non-adherent population was comparable to the S.I. of other tissue lymphocytes; however, an age-related decrease was still observed. The PHA-P proliferative response of either the 7- or 19-month non-adherent population was suppressed by the 7-month adherent population and not by the 19-month adherent population, i.e., adherent population interaction with non-adherent population decreases with age.     

Cellular Immunity in a Cutaneous Model of Cryptococcosis

The temporal development of cellular immune responses in mice inoculated cutaneously with viable Cryptococcus neoformans 145 was determined in vivo and in vitro by comparing several antigen preparations for their efficacy in the assays selected. Three antigens derived from C. neoformans 145, viz., a culture filtrate preparation (CneF-145), a membrane extract (B-HEX), and soluble cytoplasmic substances (SCS), were compared for their ability to detect delayed hypersensitivity (DH) in vivo in a footpad assay or to stimulate lymphocytes in vitro in a thymidine incorporation assay. DH to B-HEX could be demonstrated as early as 1 week after infection, whereas significant responses to SCS and CneF-145 were not regularly detected until 3 weeks after infection. Substantial reactions were observed to all three antigens up to 12 weeks, although they peaked at 2 to 3 weeks. Reactions to B-HEX and SCS were somewhat better than those to CneF. Differences in the efficacies of the three antigens were not obvious after the sixth week of infection, however. In vitro, lymph node cells from infected animals were stimulated significantly with all three antigens beginning at week 1. As with DH, however, responses to CneF-145 were usually less than those to SCS and B-HEX. In vitro lymphocyte responses waned after approximately 6 weeks, whereas DH responses were clearly positive through 12 weeks. In addition to the studies in infected animals, animals immunized with heat-killed cells of C. neoformans 145 or 184 were tested 6 to 8 days later for DH with CneF-145, CneF-184, or B-HEX derived from C. neoformans 145. The CneF-145 and CneF-184 were equally effective for detecting DH, regardless of the cryptococcal strain used for immunization. Likewise, the B-HEX detected equivalent responses in mice sensitized with each cryptococcal strain. Since all three antigens were soluble and easily extracted and since each elicited significant cellular immune responses in infected animals, further studies involving their specificity and the nature of their reactive components seems warranted as they may help evaluate immune responses in humans infected with this fungus.     

Gamma interferon production in response to homologous and heterologous strain antigens in mice chronically infected with Rickettsia tsutsugamushi.

The ability of antigen-responsive, thymus-derived lymphocytes to produce immune (gamma) interferon was investigated during the development and expression of cellular immunity to Rickettsia tsutsugamushi. C3H/HeDub mice infected subcutaneously with the Gilliam strain developed the ability to produce serum interferon in response to intravenously inoculated antigen which correlated with the development of resistance to intraperitoneal rechallenge. Antigen-responsive lymphocytes, measured by interferon production and proliferation, were first apparent in draining lymph node cells, but spleen cell responses were detectable relatively soon after the appearance of reactive lymph node cells. The peak spleen cell response was of a greater magnitude and was found to be relatively long-lived. Reactivity to heterologous strains of R. tsutsugamushi also developed after immunization and paralleled the homologous responses, although reactivity was greatest to homologous antigens. Responses to heterologous strains differed in magnitude and time of appearances; however, immune mice resisted challenge with all strains of R. tsutsugamushi tested.     

Correlates of cell-mediated immunity in Candida albicans-colonized gnotobiotic mice.

Germfree athymic (nu/nu) and euthymic (nu/+) mice were colonized with a pure culture of Candida albicans. Correlates of cell-mediated immunity (lymphocyte proliferation and footpad responses to C. albicans antigens) and in vivo clearance of mucosal infections were assessed at different time intervals after alimentary tract colonization. C. albicans hyphae infected the dorsal surface of the tongue and the cardial section of the stomach in both nu/nu and nu/+ mice within 1 week after colonization with a pure culture of C. albicans. With time after colonization and infection with C. albicans, nu/+ mice manifested positive lymphocyte proliferation and positive footpad responses to Candida antigens that appeared to correlate with the capacity to clear Candida hyphae from the dorsal surface of the tongue and in the stomach. Conversely, nu/nu mice could not clear mucosal candidosis (in the stomach and on the tongue) and did not manifest either lymphocyte proliferation or footpad swelling in response to C. albicans antigens. These studies indicated that T-cell-mediated immunity may play a role in the acquired resistance of mice to mucosal candidosis. Since neither nu/nu nor nu/+ mice developed a progressive systemic disease, T cells apparently do not play a prominent role in murine resistance to systemic candidosis of endogenous origin.     

Cell-mediated immunity in Treponema pallidum infected rabbits: in vitro response of splenic and lymph node lymphocytes to mitogens and specific antigens.

Peripheral blood lymphocytes from Treponema pallidum infected rabbits respond poorly to mitogen and specific antigens when cultured in the presence of autologous serum. Reactivity of lymphocytes from the spleen and popliteal lymph nodes of T. pallidum infected rabbits have therefore been examined by lymphocyte transformation using the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A) and extracts of T. pallidum. Spleen cell populations, both T cell enriched (by nylon wool elution) and non-nylon wool treated, which respond to T. pallidum as early as ten days post infection in normal serum, were suppressed in responses to T. pallidum when cultured in autologous serum. The same lymphocytes responded normally to PHA and Con A. Lymph node cells from infected rabbits responded normally to both T. pallidum antigen and mitogens in either autologous or normal rabbit serum. These data indicate that splenic lymphocytes are sensitive to regulatory factors in autologous serum during the early stages of T. pallidum infection whereas lymph node cells are not.     

Immunodepression in Taenia crassiceps infection: restoration of the in vitro response to sheep erythrocytes by activated peritoneal cells.

The in vitro response to sheep erythrocytes of mesenteric lymph node cells from mice infected with the larval cestode Taenia crassiceps is significantly depressed and can be restored to control levels by addition of activated peritoneal cells depleted of functional T or B lymphocytes. Adherent mesenteric lymph node cells from infected mice are unable to reconstitute the in vitro response to sheep erythrocytes of normal nonadherent cells. The responses of mesenteric lymph node cells from infected mice to the T-lymphocyte mitogens concanavalin A and phytohemagglutinin and the B-lymphocyte mitogen lipopolysaccharide are normal. Mesenteric lymph node cells from infected mice do not suppress the in vitro response to sheep erythrocytes of normal mesenteric lymph node cells. These results suggest that the immunodepression in T. crassiceps-infected mice is primarily the result of alterations in functional accessory cells.     

Specific suppression of the local GVH reaction by F1 spleen cells

The local graft-versus-host (GvH) reaction in (C57BL/6 X BALB/c) F1 hybrid mice, assayed by popliteal lymph node enlargement, was specifically depressed by an injection of parental lymphocytes mixed with spleen cells from F1 mice pretreated with the same parental lymphocytes. Suppressor activity of CBF1 spleen cells was obtained 7 days after inoculation of parental lymphocytes, and peaked on day 10. The suppressive activity was induced by only spleen cells from CBF1 which was inoculated Balb/c lymphocytes, but not C57BL/6 lymphocytes. The lymphocyte subpopulation responsible for the suppressive activity was noticed in T cell population.     

Quantitative studies on T-cell functions in MRL/MP-Lpr/Lpr mice. I. Frequency analysis of precursor cells of proliferating, cytotoxic, and T-cell growth factor-secreting T lymphocytes reveals an increase in absolute numbers, with a concomitant decrease in percentage of immunocompetent cells

A limiting dilution system has been applied to compare precursor frequencies of proliferating T lymphocytes (PTL-P), of T-cell growth factor-secreting T cells (TTCGF-P), and of cytotoxic T cells (CTL-P) in lymphocyte populations of aged, MRL/MP-lpr/lpr (MRL-lpr) mice and the congeneic strain MRL/MP- +/+ (MRL-n,), or the H-2k-compatible strains AKR/N and B10.BR responding to the mitogen concanavalin (ConA), to alloantigens (H-2) or to trinitrophenol (TNP)-modified syngeneic cells. In lymph node and spleen populations of 3- to 8-month-old MRL-lpr mice, the frequencies of H-2d- or ConA-reactive PTL-P and TTCGF-P, and of CTL-P sensitive to either H-2d, TNP, or ConA stimuli were between 5 to 30 times lower than in the corresponding populations of the other three strains. Furthermore, the frequencies of CTL-P progressively decreased in MRL-lpr mice from 3 to 8 months of age. In contrast, the absolute numbers of immunologically competent precursor T cells (PTL-P, TTCGF-P, CTL-P) was in general approximately 2- to 5-fold higher in MRL-lpr than in the control mice. However, these normal T cells do not seem to expand proportionally with the progressive lymphadenopathy in MRL-lpr mice since the number of T lymphocytes recovered from lymph nodes of the individual animals tested exceeded those of tissues from control mice by 30- to 300-fold. The results therefore suggest that mature T cells are progressively diluted out by abnormal lymphocytes in lymphocyte populations of aging MRL-lpr mice, thus causing a decrease of immune responses in vitro and possibly also affecting optimal cellular interactions in vivo.     

Statins inhibit lymphocyte homing to peripheral lymph nodes

Lymphocyte homing to peripheral lymph nodes is governed by adhesion molecules, including lymphocyte function-associated antigen 1 (LFA-1). Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and exert anti-inflammatory effects, e.g. inhibition of LFA-1. It is still not known whether statin compounds are capable of inhibiting lymphocyte homing in vivo. We used a cervical lymph node preparation to study the effects of simvastatin on lymphocyte adhesion to high endothelial venules (HEVs) by means of intravital fluorescence microscopy (IVM). IVM revealed that firm adhesion of lymphocytes to HEV endothelium critically depends on the adhesive function of LFA-1. The number of firmly adherent lymphocytes was reduced by 58% in LFA-1-deficient mice (P < 0.05 versus wild-type controls). As in mutant mice, acute treatment with simvastatin (i.p. injection at 2 hr prior to IVM) inhibited the firm adhesion of lymphocytes to HEV endothelium of wild-type animals by 63% (P < 0.05 versus vehicle-treated wild-type controls). In addition, acute treatment with the synthetic statin-derivate LFA878 also reduced firm lymphocyte adhesion in HEVs by 63% (P > 0.05 versus placebo-treated controls). Histological analysis after a 10-day treatment with simvastatin showed reduced cellularity of cervical lymph nodes, as indicated by a reduction of the relative area of haematoxylin-stained cell nuclei in cervical lymph node cross-sections from 94 +/- 0% in vehicle-treated controls to 77 +/- 3% in simvastatin-treated mice (P < 0.05). We conclude that statin compounds are capable of inhibiting lymphocyte homing to murine peripheral lymph nodes in vivo. This may have novel implications for the treatment of adaptive immune responses, e.g. transplant rejection.     

Individual differences in the orientation of the cytolytic T cell response against mouse tumor P815

We reported previously that the mouse tumor P815 expresses four distinct antigens (A, B, C, D) recognized by syngeneic cytolytic T lymphocytes (CTL). A fifth P815 antigen (E) was identified by means of a CTL clone derived from tumor-infiltrating lymphocytes. We compared a number of mice for the orientation of their CTL response with respect to the various P815 antigens. Lymphocytes from mice inoculated subcutaneously with living P815 cells were stimulated in vitro with tumor cells and the resulting CTL were tested against targets expressing either antigens A and B or antigens C, D and E. Many mice had an asymmetrical response, some producing CTL directed almost exclusively against antigens A, B and others producing CTL directed almost exclusively against C, D. E. When mice were inoculated into two separate sites, different orientations in the responses of the two local lymph nodes were often observed, suggesting that individual differences in the orientation of the anti-P815 CTL response do not result from preexisting differences between the animals. Asymmetrical CTL responses persisted in mice that were given a second injection of tumor cells. A possible interpretation of our results is that the major component of the CTL response is made of the progeny of a very small number of CTL precursors that happen to be the first to be stimulated by the tumor antigens.     

Increased inducible apoptosis in CD4+ T lymphocytes during polymicrobial sepsis is mediated by Fas ligand and not endotoxin

Recent studies suggest that increased lymphocyte apoptosis (Ao) detected in peripheral blood T cells from burn patients appears to contribute to decreased lymphocyte immunoresponsiveness. However, while it is known that sepsis induces a marked depression in the splenocyte immune response (i.e. decreased interleukin-2, interferon-gamma production and proliferation) in response to the T-cell mitogen concanavalin A (Con A), it is unknown whether this depression is associated with an increase in inducible Ao and if so, which mediators control this process. To assess this, splenocytes were harvested from mice at 24 hr (a period associated with decreased Con A response) after the onset of polymicrobial sepsis [caecal ligation and puncture (CLP)] or sham-CLP (Sham) and then stimulated with 2.5 microg Con A/ml (24 hr). Septic mouse splenocytes stimulated with Con A, while not showing a change in their phenotypic make-up, did exhibit a marked increase in the percentage of splenocyte that were Ao+ which was associated with altered cytokine release. This appears to be due to an increase in the percentage of Ao+ cells in the CD4+ CD8- population and was associated with enhanced Fas antigen expression as well as an increase in mRNA for the Fas-FasL gene family. To determine if the changes in Ao are due to either endotoxin (a product of Gram-negative bacteria seen in CLP mice) or the expression of Fas ligand (FasL; a mediator of activation-induced lymphocyte Ao), a second set of studies examining Con A-inducible Ao was performed with splenocytes harvested from septic endotoxin-tolerant C3H/HeJ and the FasL-deficient C3H/HeJ-Fasl gld mice. The results show that increased splenocyte Ao detected following CLP is due to a FasL-mediated process and not to endotoxin. Thus the inadvertent up-regulation of FasL-mediated splenocyte Ao may contribute to the depression of splenocyte immune responses seen during polymicrobial sepsis.     

The effect of neonatal thymectomy on the ontogeny of mitogen responses in the quokka (Setonix brachyurus)

The lymphocyte responses to phytohaemagglutinin (PHA), Concanavalin A (Con A), and Pokeweed mitogen (PWM) were determined at various intervals throughout pouch life in the quokka (Setonix brachyurus). The responses to both PHA and Con A of lymphocytes from the blood and mesenteric lymph node of thymectomised pouch young were significantly depressed, indicating that these mitogens stimulate thymus-dependent lymphocytes. In contrast to most other vertebrates, splenic leucocytes from intact pouch young responded poorly to stimulation with these mitogens: after neonatal thymectomy the responses were slightly, but not significantly, depressed. Peripheral blood lymphocytes from thymectomised quokkas showed a significantly decreased responsiveness to PWM at 100 and 140 days of age, but the response of lymphocytes from other sources was not significantly different from that of intact animals at comparable ages. There were no significant trends with age in the mitogen responses of lymphocytes from thymectomised pouch young. These data are discussed in relation to the spontaneous restoration of immune responsiveness which occurs after the end of reserves of immunocompetent lymphocytes which had been built up.     

Hyperactive T-cell function in young NZB mice; increased proliferative responses to allogenic cells.

The one-way mixed lymphocyte reaction was employed to study proliferative responses to antigens by mature, immunocompetent T cells from NZB mice 3 weeks to 4 months old. Compared to cells from control mice of the same H-2 type, thymus, spleen and lymph node cells from NZB mice were hyperactive in this response. The results are discussed in relation to possible effects of chronic stimulation by endogenous type C leukaemia virus upon differentiation of functional T cells or upon regulation by T cells of other T-cell functions, including augmentation of antibody responses.     

Effects of cyclophosphamide on murine candidiasis.

Male CBA/J mice were given a single dose of 200 mg of cyclophosphamide (CY) per kg 3 days before a first or second cutaneous inoculation with viable Candida albicans in an attempt to suppress antibody formation and determine the effects of such suppression on the development of acquired immunity. After cutaneous inoculation, mice not treated with CY developed acquired immunity to intravenous challenge, which was accompanied by the development of circulating antibodies, delayed hypersensitivity, and in vitro responsiveness of lymph node cells to Candida antigens. CY treatment resulted in an immediate depression of peripheral blood leukocytes, with polymorphonuclear leukocytes and monocytes rebounding quickly to normal or above normal levels while lymphocyte remained depressed throughout the 4-week observation period. In vitro stimulation of lymph node cells from CY-treated mice was depressed shortly after treatment; however, responses to phytohemagglutinin and three Candida antigens (a cell wall preparation, a membrane preparation, and soluble cytoplasmic substances) recovered, whereas the responses to lipopolysaccharide did not. CY effects on the cutaneous lesion were twofold; first, the number of viable Candida cells in the lesions was much higher in animals receiving CY 3 days before Candida inoculation, and second, the size of the dermal lesion was either greatly enhanced or reduced depending upon the time of CY treatment relative to the number of cutaneous Candida inoculations. CY-treated animals developed higher levels of delayed hypersensitivity to the membrane preparation when infected once cutaneously than did corresponding untreated animals. The number of mice responding with circulating antibodies to soluble cytoplasmic substances after cutaneous inoculation was greatly reduced in CY-treated groups, and this impaired ability to produce antibodies correlated with the poor survival of these mice after intravenous challenge. Our results suggest that the ability to produce antibody at the time of challenge is crucial to successful defense against systemic candidiasis in this murine model.     

Cell-mediated immunity in experimental murine dermatophytosis. I. Temporal aspects of T-suppressor activity caused by Trichophyton quinckeanum.

Cutaneous dermatophyte infections caused by Trichophyton quinckeanum were established in various strains of mice. All congenic BALB/B (H-2b), BALB/c (H-2d) and BALB/K (H-2k) strains showed high susceptibility to dermatophyte infection. Susceptibility is independent of MHC phenotype, since other strains with corresponding H-2 haplotypes such as C57BL/6 (H-2b), DBA/2 (H-2d) and CBA (H-2k) were resistant to the disease. During the acute phase of infection in BALB/c mice, the in vitro blastogenic responses of regional lymph node cells was suppressed. Suppression was observed for both the T cell mitogens concanavalin A and phytohaemagglutinin, and for the B cell mitogen lipopolysaccharide. A series of cell-mixing experiments revealed that lymph node cells from infected mice were able to suppress the T cell and B cell mitogenic responses of lymph node cells from normal mice. Suppression was mediated by T cells and abrogated by treatment of lymph node cells with either monoclonal anti-thy-1.2 or anti-Ly-2.2 and complement. In this report, we discuss the possibility that T-suppressor mechanism mediated by cells bearing the Ly-2+ phenotype and activated during dermatophyte infection may determine the course of the disease.