Diversity of human alpha beta T cell receptors.
Explore the source record for details and available documents.
Binding Sites↗
Biomedical subjects
T P Arstila
Publications and source records attributed to T P Arstila.
Identical T cell clones are located within the mouse gut epithelium and lamina propia and circulate in the thoracic duct lymph.
Murine gut intraepithelial (IEL) T cell receptor (TCR)-alpha/beta lymphocytes bearing CD8alpha/13 or CD8alpha/alpha coreceptors have been shown previously to express different oligoclonal TCR beta chain repertoires in the same mouse, in agreement with other evidence indicating that these two populations belong to different ontogenic lineages, with only CD8alpha/beta+ IELs being fully thymus dependent. CD8alpha/beta+, but not CD8alpha/alpha+, T lymphocytes are also present in the lamina propria. Here, we show that CD8alpha/beta+ lymphocytes from the lamina propria and the epithelium are both oligoclonal, and that they share the same TCR-beta clonotypes in the same mouse, as is also the case for CD4alpha T cells. Furthermore, identical T cell clones were detected among CD8alpha/beta IELs and CD8alpha/beta+ blasts circulating into the thoracic duct (TD) lymph of the same mouse, whereas TD small lymphocytes are polyclonal. These findings must be considered in light of previous observations showing that T blasts, but not small T lymphocytes, circulating in the TD lymph have the capacity of homing into the gut epithelium and lamina propria. These combined observations have interesting implications for our understanding of the recirculation of gut thymus-dependent lymphocytes and their precursors, and of the events leading up to the selection of their restricted TCR repertoire.
Animals↗
A direct estimate of the human alphabeta T cell receptor diversity.
Generation and maintenance of an effective repertoire of T cell antigen receptors are essential to the immune system, yet the number of distinct T cell receptors (TCRs) expressed by the estimated 10(12) T cells in the human body is not known. In this study, TCR gene amplification and sequencing showed that there are about 10(6) different beta chains in the blood, each pairing, on the average, with at least 25 different alpha chains. In the memory subset, the diversity decreased to 1 x 10(5) to 2 x 10(5) different beta chains, each pairing with only a single alpha chain. Thus, the naïve repertoire is highly diverse, whereas the memory compartment, here one-third of the T cell population, contributes less than 1 percent of the total diversity.
Adult↗
Expression of chL12 surface antigen is associated with cell survival in the avian bursa of Fabricius.
During B-cell development in the avian bursa of Fabricius most of the developing B cells die by apoptosis and only a minority survive to emigrate into the periphery. Recently, it has been shown that when developing bursal cells become mature and ready to migrate they start to express chL12 antigen. The expression of this cell-surface molecule was found to be associated with the survival of the bursal cells both after in vitro culture and after in vivo cyclophosphamide (CY) treatment. The frequency of early apoptotic cells in freshly isolated bursal cells was found to be high. The high susceptibility of these cells to apoptosis is in line with the finding of low bcl-2 mRNA expression. We conclude that expression of avian chL12 antigen is associated with the survival of bursal cells.
Animals↗
Costimulatory function of CD28 in avian gammadelta T cells is evolutionarily conserved.
CD28 costimulatory signals are required for T-cell proliferation and lymphokine production. In this work, the functional conservation of CD28 was studied in avian gammadelta T cells. The avian CD28 molecule is expressed on all alphabeta T cells and is capable of giving a costimulatory signal. Most peripheral gammadelta T cells are CD28 negative; however, we identified a CD28-positive gammadelta T-cell subset from peripheral blood comprising about 12% of gammadelta T cells. The peripheral CD28+ gammadelta T-cell subset included all CD8+ gammadelta T cells known to be a responding subset during activation. After polyclonal activation, the frequency of CD28+ gammadelta T cells was increased and the activation also up-regulated CD5, CD25 and major histocompatibility complex (MHC) class II molecules. These changes were detected after both polyclonal and antigen-specific T-cell activation. In addition, we also showed that CD28 can give a costimulatory signal to gammadelta T cells and that this signal leads to up-regulation of IL-2 and bcl-x transcripts. These results indicate that the function of CD28 is evolutionarily conserved and can already be detected in avian gammadelta T cells.
Animals↗
T cell subsets and the activation of gamma delta T cells.
Explore the source record for details and available documents.
Animals↗
Primed avian gamma delta T cells respond to mycobacterial antigens, but show no preference for the 65-kDa heat shock protein.
We have studied the reactivity of chicken T cells to mycobacterial antigens. Neither peripheral blood nor splenic lymphocytes isolated from unprimed chickens proliferated in response to mycobacterial antigens (mycobacterial sonicate, purified protein derivative, or recombinant 65-kDa heat-shock protein HSP65). After immunization with complete Freund's adjuvant (CFA) a strong response appeared, and a transient increase of peripheral blood gamma delta T cells was observed. Analysis of spleen cells isolated from CFA-primed chickens showed that both alpha beta and gamma delta T cells were activated by the mycobacterial antigens, apparently at equal levels. Both subsets also responded to HSP65, but no preference of gamma delta T cells to respond to it or any of the other mycobacterial antigens was observed. These results indicate that although HSP65 is an important mycobacterial antigen, it is not dominant in the chicken gamma delta T cell repertoire. Moreover, the results show a clear distinction between the naive and primed repertoire of gamma delta T cells.
Animals↗
Gamma delta and alpha beta T cells are equally susceptible to apoptosis.
Little is known about the role of apoptosis in the regulation of gamma delta T cell development and function. We have used chicken as a model to study apoptosis of gamma delta T cells at different stages of their development. Apoptosis was measured with electrophoretic analysis of DNA fragmentation and flow cytometric determination of DNA content combined with immunofluorescence staining of cell surface molecules. In vitro culture, dexamethasone, and gamma-irradiation induced apoptosis of both gamma delta TCR+ thymocytes and peripheral gamma delta T cells. Apoptosis could be induced even in the earliest thymic gamma delta thymocytes on embryonic day 13. Resting peripheral blood gamma delta T cells were more resistant to apoptosis than thymocytes and spleen cells. Following polyclonal activation of splenic gamma delta T cells by Con A, the proportion of the CD8+ gamma delta T cell blasts decreased significantly when recultured without further stimulation. These results indicate that gamma delta T cells are susceptible to apoptosis in a manner similar to alpha beta T cells, and suggest that apoptosis plays an important role in the regulation of the development and function of both thymic and peripheral gamma delta T cells.
Animals↗
Evolutionarily conserved function of CD28 in alpha beta T cell activation.
The functional role of the chicken homologue of CD28 was studied. It is expressed on all thymocytes, and both V beta 1- and V beta 2-family expressing peripheral alpha beta T cells. Peripheral gamma delta T cells are CD28-negative. Monoclonal antibody against CD28 had a costimulatory effect on T cells stimulated by phorbol myristate acetate (PMA), concanavalin A or MoAb against TCR. V beta 1 and V beta 2 expressing cells responded equally well to stimulation with anti-CD28 in combination with PMA. These responses were resistant to cyclosporin A, but inhibited by herbimycin A, suggesting that CD28 employs a signalling pathway at least partly distinct from that triggered by TCR/CD3. These data indicate a striking conservation of the costimulatory function of CD28 and emphasize the importance of this costimulatory pathway.
Animals↗
Central role of CD4+ T cells in avian immune response.
Chicken alpha beta T cells express either CD4 or CD8 accessory molecules, whereas most of the gamma delta T cells do not. The functional significance of the alpha beta T cells is relatively well understood. The CD4+ alpha beta T cells function as coordinators of the immune response, and CD8+ alpha beta T cells are the effector cells in cytotoxic responses, killing infected target cells. In comparison, the role of gamma delta T cells is so far poorly known. In chicken, the gamma delta T cells comprise a large lymphocyte subset. They can be induced to proliferate by various stimuli, but the proliferative response is dependent on CD4+ alpha beta T cells. The CD4+ T cells are also essential for the generation of antibody responses by providing help for the B cells and can influence cytotoxic responses as well. Thus, the CD4+ alpha beta T cells have a central role in the avian immune system, and their activation is a prerequisite for responses by other types of cells, including gamma delta T cells.
Animals↗
Androgen-induced expression of the peripheral blood gamma delta T cell population in the chicken.
Unlike alpha beta T cells, the physiologic significance of gamma delta T cells has remained elusive. In avian species they comprise a large circulating T cell subset. Here we report that in chicken around the time of sexual maturation (4 to 6 mo of age) a significant increase of the gamma delta T cells takes place in male but not in female chickens. The frequency of gamma delta T cells increases both in peripheral blood and spleen, but not in intestinal epithelium. This expansion is independent of MHC haplotype, being observed in various inbred and MHC-recombinant strains. Furthermore, administration of testosterone to young female chickens induces an equivalent increase in the frequency of gamma delta T cells in peripheral blood. These results indicate that sex, through androgens, has an effect on the gamma delta T cell numbers in a species, in which these cells form a major subset of peripheral lymphocytes.
Animals↗
Helper activity of CD4+ alpha beta T cells is required for the avian gamma delta T cell response.
We have studied the in vitro activation of chicken gamma delta T cells. Both splenic alpha beta and gamma delta T cells obtained from complete Freund's adjuvant-primed chickens proliferated in vitro when stimulated with mycobacterial sonicate or purified protein derivative of Mycobacterium tuberculosis. When CD4+ cells or alpha beta T cell receptor (TcR)-positive cells were removed, both the proliferation and the blast formation of gamma delta T cells in response to mycobacterial antigens were abrogated. The response was restored if supernatant from concanavalin A (Con A)-activated lymphocyte cultures (CAS) as a source of helper factors was added together with the specific antigen purified protein derivative. The CD4- or alpha beta TcR-depleted cells still proliferated in response to Con A, although a decrease of the response was observed. To analyze the gamma delta T cell response more specifically we stimulated peripheral blood cells with immobilized monoclonal antibodies against T cell receptor. Anti-gamma delta TcR antibody alone did not induce significant proliferation. When CAS was added together with the anti-gamma delta TcR monoclonal antibody, a strong proliferation of gamma delta T cells was observed. In contrast, both V beta 1- and V beta 2-expressing alpha beta T cells proliferated in vitro in response to stimulation with the relevant anti-TcR monoclonal antibody alone. Depletion of either V beta 1+ or V beta 2+ T cell subset alone had no negative effect on the proliferation or blast formation of gamma delta T cells stimulated with mycobacterial antigens. Taken together our results suggest that CD4+ alpha beta T cells (both V beta 1- and V beta 2-expressing) play a role in the activation and response of chicken gamma delta T cells.
Animals↗
Application of the polymerase chain reaction and immunofluorescence techniques to the detection of bacteria in Yersinia-triggered reactive arthritis.
Leukocytes in synovial fluid and peripheral blood samples from patients with Yersinia-triggered reactive arthritis were analyzed after DNA amplification using the polymerase chain reaction. The primers applied were specific for the virulence plasmid-coded 1crE genes of Yersinia enterocolitica O:3 and Yersinia pseudotuberculosis III. No Yersinia DNA was observed within the synovial fluid cells or peripheral blood cells by polymerase chain reaction techniques. However, Yersinia antigens were detected in the synovial fluid cells by immunofluorescence techniques. These results suggest that only parts of the causative agents, not the entire microbe, can enter the joint and initiate the inflammation that leads to a reactive arthritis.
Adolescent↗