Biomedical subjects

Charles A Janeway

Publications and source records attributed to Charles A Janeway.

22 records · Page 2Linked to original sources

PubMed2002

Self-recognition and the biased mature repertoire in TCR beta transgenic mice: the exception that supports the rule.

Detailed sequence analysis of the companion alpha chains in several T-cell receptor (TCR) beta chain transgenic mice have shown that the mature alpha chain repertoires of CD4+ T cells are biased toward the parental TCR alpha chain sequences. These studies further indicate that it is self-peptide-self-MHC recognition during positive intrathymic selection that biases the structure of the mature TCR alpha chain repertoire. To further establish the causative relationship, it is important to examine whether such a bias can be abolished when positive selection is absent. The human collagen IV-I-A(s) complex-specific KB TCR cannot be positively selected on the self-peptide-self-MHC complexes present in the I-A(s) strain. Therefore, the KB TCR beta chain transgenic mice offer a unique opportunity for addressing this issue.

Animals↗

PubMed2001

A trip through my life with an immunological theme.

In this essay, I make four points about the operation of the immune system. First, thanks to the innate immune system's regulation of the main costimulatory molecules CD80 and CD86, the immune system rarely mistakes a pathogen for a self-antigen. Second, the adaptive immune system consisting of T lymphocytes and B lymphocytes can mistake self for non-self because adaptive immunity is selected in single somatic cells. Third, the adaptive immune system of T lymphocytes and B lymphocytes is always referential to self, as it is selected on self-ligands; it persists in the periphery on self-ligands; and at least for T cells, it is dependent on self-ligands to be able to mount a response. Fourth, it is becoming clear that regulatory or suppressor T cells are our main defense against autoimmunity, as my first boss, Richard Gershon, had predicted. These cells recognize antigen as do all T cells, but they secrete the immunoregulatory cytokines IL-10 and TGF beta.

Allergy and Immunology↗

PubMed2001

Innate immune recognition.

The innate immune system is a universal and ancient form of host defense against infection. Innate immune recognition relies on a limited number of germline-encoded receptors. These receptors evolved to recognize conserved products of microbial metabolism produced by microbial pathogens, but not by the host. Recognition of these molecular structures allows the immune system to distinguish infectious nonself from noninfectious self. Toll-like receptors play a major role in pathogen recognition and initiation of inflammatory and immune responses. Stimulation of Toll-like receptors by microbial products leads to the activation of signaling pathways that result in the induction of antimicrobial genes and inflammatory cytokines. In addition, stimulation of Toll-like receptors triggers dendritic cell maturation and results in the induction of costimulatory molecules and increased antigen-presenting capacity. Thus, microbial recognition by Toll-like receptors helps to direct adaptive immune responses to antigens derived from microbial pathogens.

Adaptation, Physiological↗

PubMedDate not supplied

Expression of transgene encoded TGF-beta in islets prevents autoimmune diabetes in NOD mice by a local mechanism.

To analyse the effects of TGF-beta in insulin dependent diabetes mellitus (IDDM), we have developed non-obese diabetic (NOD) transgenic mice expressing TGF-beta under the control of the rat insulin II promoter. Pancreata of TGF-beta transgenic mice were roughly one twentieth of the size of pancreata of wild-type NOD mice and showed small clusters of micro-islets rather than normal adult islets. However, these islets produced sufficient levels of insulin to maintain normal glucose levels and mice were protected from the diabetes, which developed in their negative littermates. A massive fibrosis was seen in the transgenic pancreata that was accompanied with infiltration of mononuclear cells that decreased with age. Interestingly, these mice showed normal anti-islet immune response in their spleens and remained susceptible to adoptive transfer of IDDM by mature cloned CD8 effector cells. TUNEL assays revealed increased apoptosis of invading cells when compared to non-transgenic NOD mice. Taken together, these results suggest that TGF-beta protects islets by a local event.

Animals↗