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V Udhayakumar

Publications and source records attributed to V Udhayakumar.

47 records · Page 3Linked to original sources
PubMed1990

Macrophages but not B cells from aged mice are defective in stimulating autoreactive T cells in vitro.

In the present study the effect of aging on the capacity of Ia+ cells to stimulate autoreactive T cells in the syngeneic mixed lymphocyte reaction (SMLR) was investigated. Using young CD4+ T cells as responders, it was observed that unseparated whole spleen cells from aged mice had normal stimulatory activity comparable to that of young spleen cells. Interestingly, however, when purified splenic adherent cells (SAC) enriched for macrophages or splenic B cells were used as stimulators, aged SAC but not aged B cells were found to be defective in stimulating autoreactive T cells. This defect in aged SAC was not due to decreased expression of Ia antigens since the percentage of Ia+ SAC and density of Ia antigen expression was similar in both young and old mice. Also, the B cells from aged mice expressed normal levels of Ia antigens. Aged SAC, when mixed with young SAC could also actively suppress the normal SMLR. However, this suppression was not due to increased prostaglandin production but was found to be associated with interleukin-1 (IL-1) regulation, inasmuch as addition of exogenous IL-1 could completely reconstitute the defective stimulatory activity of aged SAC and also abolished the suppressor activity of the SAC. Aged mice also demonstrated an intrinsic defect in the CD4+ T cells responding in the SMLR. Together, our studies on the SMLR demonstrate an age-related defect in responder autoreactive T cells and in stimulator splenic macrophages but not in the stimulatory activity of B cells.

Aging↗
PubMed1989

Isolation and immunological characterization of a group of new B lymphomas from CBA mice.

We have isolated and characterized a new series of B lymphoma which occurred spontaneously in a group of CBA/N mice that were transferred with spleen or lymph node cells from 24-month-old CBA/Ca mice. Tumor cell lines from six CBA/N mice that received spleen cells were rescued and designated as BKS-2, BKS-3, BKS-4, BKS-5, BKS-6, and BKS-7. Also, tumor cells from a recipient of lymph node cells were rescued and the resulting cell line was designated BKL. These tumor cells expressed membrane immunoglobulin (mu, kappa), major histocompatibility complex Class I and Class II molecules, B220, Lyb8, Fc receptors, J11d, interleukin 2 receptors, and Ly1. All of the tumors did not express the T cell specific markers Thy 1.2, L3T4, and Lyt2.1. They appeared to be clonal in origin, since they exhibited common rearrangements at both heavy and light chain immunoglobulin loci. Phenotypically, these lymphomas appeared to be analogous to immature B cells. Also, these lymphomas displayed different functional reactivities when treated with various B cell mitogens and growth factors in vitro. Anti-mu antibodies which normally induce B cell growth inhibited the proliferation of these lymphoma cells in vitro, whereas they responded to lipopolysaccharide, T cell-derived growth factors, and interleukin 5 by enhanced proliferation. These tumor cells expressed constitutively high levels of c-myc mRNA.

Animals↗
PubMed1989

Protective immunity induced by porin against Salmonella infection in mice.

Porin, a major outer membrane protein was purified from Salmonella typhimurium and its immune potential was studied in mice. Active immunization with porin induced about 45 per cent protection to an intravenous challenge with 10LD50 of S. typhimurium. Further, in porin immunized mice significant level of anti-porin antibodies and DTH reaction were detected. Attempts were also made to improve the immune potential of porin. Freund's complete adjuvant when mixed with immunogenic doses of porin enhanced the anti-porin antibody titre. However, it could not improve the protective ability of porin. On the other hand, porin when injected along with lipopolysaccharide (LPS) induced a higher level (55% survival with 50LD50) of protection than porin or LPS alone. This finding was also substantiated by the significantly reduced in vivo growth of challenge organisms in mice immunized with porin plus LPS. These results indicate that porin is a protective antigen and LPS significantly enhances the protective ability of porin.

Animals↗
PubMed1988

Impaired autoreactive T cell-induced T cell-T cell interaction in aged mice.

Self-Ia-reactive (autoreactive) L3T4+ T cell clones have been shown earlier to stimulate the proliferation of syngeneic naive L3T4+ T cells and initiate a T cell-T cell (T-T) interaction leading to the generation of immunoregulatory circuits. Since aging has been shown to be associated with a decline of the immune responsiveness, age-related alterations in the T-T interaction was investigated in the present study. Using several I-Ed-specific autoreactive T cell clones isolated from 2- to 3-month-old (young) DBA/2 mice as stimulators, it was observed that L3T4+ T cells from 22- to 24-month-old (aged) DBA/2 mice, failed to demonstrate a significant response to the autoreactive T cells. In contrast, L3T4+ T cells from young mice responded strongly to the autoreactive T cell clones. The deficient T-T cell interaction in aged mice correlated with an impaired syngeneic mixed lymphocyte reaction in these mice, thereby suggesting that aging induces a defect both in the autoreactive T cells and in T cells which react with the autoreactive T cells. When exogenous recombinant interleukin 2 (rIL-2), recombinant interleukin 4 (rIL-4), or a combination of these was added to the interaction, it was observed that rIL-4 but not rIL-2 enhanced the T-T interaction in young mice. However, rIL-4 or a combination of rIL-2 and rIL-4 failed to correct the defective T-T interaction in aged mice. Since the T cell network is believed to play an important role in the maintenance of normal immune system homeostasis, the present study suggests that age-related alterations in T and B cell functions and increased susceptibility to autoimmune diseases with age may result from a defect in the T cell network regulation.

Aging↗
PubMed1988

Physiology of murine B lymphocytes. I. Life-spans of anti-mu and haptenated Ficoll (thymus-independent antigen)-reactive B cells.

We have evaluated the life-span of B lymphocytes by measuring the functional reactivity of normal B cells upon transfer into xid mice, which do not respond to anti-mu, fluoresceinated-Ficoll (FL-Ficoll) and 2,4,6-trinitrophenyl aminoethylcarbamylmethyl Ficoll (TNP-Ficoll). After 4 days of transfer only 30-40% of anti-mu-reactive cells decayed leaving behind 60-70% of B cells which appeared to decay slowly. Even 10 days after transfer approximately 40% of anti-mu-reactive B cells can be recovered from the recipients. This result demonstrates the existence of heterogeneity in the life-spans of anti-mu-reactive B lymphocytes and that a major population (60-70%) of B cells persists beyond 4 days. Interestingly, the short-lived B cell subpopulation was not detected when the decay of the antigen-specific B cells was studied. Thus, TNP-Ficoll and FL-Ficoll-reactive B cells were found to be long lived and such B cells did not decline at all, even 5 months after transfer into xid mice.

Animals↗
PubMed1987

Protective immunity induced by outer membrane proteins of Salmonella typhimurium in mice.

Outer membrane proteins (OMP) extracted from both smooth (C5) and rough (Rb2) strains of Salmonella typhimurium were able to induce protective immunity to salmonellosis. The OMP-induced protection lasted for at least 6 months. The antibody level was estimated by passive hemagglutination. In the C5 OMP-immunized mice, antibodies to both proteins and lipopolysaccharide were detected. On the other hand, in the Rb2 OMP-immunized mice, antiprotein but not antilipopolysaccharide antibodies were detected. Delayed-type hypersensitivity appeared as early as the second week after immunization with OMP and persisted through the fourth week.

Animals↗
PubMed1987

An outer membrane protein (porin) as an eliciting antigen for delayed-type hypersensitivity in murine salmonellosis.

The porin, an outer membrane protein of Salmonella typhimurium, was found to be a suitable antigen for eliciting delayed-type hypersensitivity in mouse salmonellosis. Histological examination of the reaction site revealed that the porin was superior to other antigenic preparations in eliciting a typical delayed-type hypersensitivity reaction consisting of mononuclear cell infiltration without polymorphonuclear cell contamination. This study indicates the importance of using a suitable protein antigen from S. typhi for human application.

Animals↗
PubMed1985

Role of outer membrane proteins in immunity against murine salmonellosis--1. Antibody response to crude outer membrane proteins of Salmonella typhimurium.

The humoral immune response to crude outer membrane proteins (comp) of S. typhimurium in mice has been characterized. Maximal and quicker antibody response was observed when 50 micrograms of comp was injected intraperitoneally. The comp of smooth C5 strain of S. typhimurium evoked antibody response to both lipopolysaccharide (LPS) and proteins. Absorption of these sera with LPS coated erythrocytes eliminated the antibodies to LPS completely, while the antibody level to protein was left unaltered. The comp from rough mutant (lacking O-specific chain of LPS) of S. typhimurium elicited antibodies to proteins but not to LPS. These results indicate the concomitant production of antibodies to Salmonella outer membrane proteins also. The significance of such antibodies in protection and diagnosis has been discussed.

Animals↗
PubMedDate not supplied

Immunogenicity of Plasmodium falciparum and Plasmodium vivax circumsporozoite protein repeat multiple antigen constructs (MAC).

In this study we characterized the immunogenic properties of three different multispecies multiple antigen constructs (MACs) carrying the circumsporozoite protein (CSP) repeats of human malaria parasites, Plasmodium falciparum and P. vivax. We synthesized tetrameric MACs containing the antigenic repeats from the CSP of P. vivax-like parasite in two arms and CSP repeat sequences of either P. vivax type-1 (vivax-like/vivax type-1 MAC), P. vivax type-2 (vivax-like/vivax type-2 MAC), or P. falciparum (vivax-like/falciparum MAC) in the other two arms. Mice of four different genetic backgrounds (H-2a, H-2b, H-2d, and H-2k) were immunized with these MACs in Freund's adjuvant. All three MAC preparations were found to elicit antibodies to P. vivax-like CSP repeats in B10.BR, B10.A, and C57BL/6 mice. On the other hand, in B10.D2 mice only vivax-like/vivax type-1 MAC, but not the other two MACs induced antibodies to the P. vivax-like CSP repeats. In mice immunized with vivax-like/vivax type-1 MAC, antibodies to P. vivax type-1 CS repeat peptides were induced in B10.BR, B10.A, and C57BL/6 mice, but not in B10.D2 mice. Antibody responses to P. vivax type-2 repeats were not induced in any of the four strains of mice that were immunized with vivax-like/vivax type-2 MAC. While B10.BR, B10.A, and C57BL/6 mice produced antibodies to NANP repeats of P. falciparum CSP following immunization with vivax-like/falciparum MAC, B10.D2 mice failed to elicit antibodies to this repeat. All the sera that showed positive reactivity to peptides in enzyme-linked immunosorbent assay were found to react with sporozoites by IFA. In conclusion, these results showed that naturally immunogenic epitopes from different species of malaria parasites can be incorporated in a single vaccine construct to induce immune responses against multiple epitopes.

Amino Acid Sequence↗