Functional Specialization of Memory Th Cells Revealed by Expression of Integrin CD49b

Kassiotis, George; Gray, David; Kiafard, Ziba; Zwirner, Jörg; Stockinger, Brigitta

doi:10.4049/jimmunol.177.2.968

Cited by 41 publications

(39 citation statements)

References 46 publications

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“…Interestingly, though a large proportion of T cells in the lung express CD49b, administration of blocking Abs to CD49b did not appear to affect either the CD4 or the CD8 T cell numbers in the lung or lymphoid tissues (data not shown). The latter finding is supported by the recent observation that adoptively transferred CD49a ϩ and CD49b Ϫ CD4 T cells homed equally well to an influenza infected lung (38). This suggests that CD49b (VLA-2) may not function in a manner analogous to CD49a (VLA-1) in regulating the retention of memory T cells in the extralymphoid space.…”

Section: Discussionmentioning

confidence: 68%

“…For example, the observation that more CD4 ϩ T cells in the lung expressed CD49b, and fewer expressed CD49a prevailed whether the cells were primed by viral infection or Th2-inducing conditions. This is at odds with the simple interpretation that CD49b expression correlates with Th1 and Th2 phenotypes among CD4 T cells (38,39). Similar expression of CD49a and CD49b was observed on CD8 ϩ T cells responding to lymphocytic choriomeningitis virus infection in the spleen (40).…”

Section: Discussionmentioning

confidence: 98%

“…The observations also have implications for the regulation of allergic responses because the trafficking and retention of allergenspecific T cells in the lung could be viewed to have detrimental effects upon Ag re-encounter. Recent work suggests that CD49b is stably expressed on a subset of CD4 ϩ memory T cells, suggesting that these are a population of memory T cells completely distinct from the CD49b negative subset (38). It is not known to what extent collagen integrin-negative memory T cells can convert to collagen integrin-positive cells during the resting memory phase.…”

Section: Discussionmentioning

confidence: 99%

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Collagen Distribution and Expression of Collagen-Binding α1β1 (VLA-1) and α2β1 (VLA-2) Integrins on CD4 and CD8 T Cells during Influenza Infection

Richter

Ray

Chapman

et al. 2007

The Journal of Immunology

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Most viral infections occur in extralymphoid tissues, yet the mechanisms that regulate lymphocytes in these environments are poorly understood. One feature common to many extralymphoid environments is an abundance of extracellular matrix. We have studied the expression of two members of the β1 integrin family of collagen-binding receptors, α1β1 and α2β1 (CD49a, VLA-1 and CD49b, VLA-2, respectively), on CD4 and CD8 T cells during the response to influenza infection in the lung. Flow cytometry showed that whereas T cells infiltrating the lung and airways can express both CD49a and CD49b, CD49a expression was most strongly associated with the CD8+ subset. Conversely, though fewer CD4+ T cells expressed CD49a, most CD4+ cells in the lung tissue or airways expressed CD49b. This reciprocal pattern suggested that CD4 and CD8 T cells might localize differently within the lung tissue and this was supported by immunofluorescent analysis. CD8+ cells tended to localize in close proximity to the collagen IV-rich basement membranes of either the airways or blood vessels, whereas CD4+ cells tended to localize in the collagen I-rich interstitial spaces, with few in the airways. These observations suggest that CD4 T cell interaction with the tissue microenvironment is distinct from CD8 T cells and support the concept that CD4+ T cells in peripheral tissues are regulated differently than the CD8 subset.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Collagen Distribution and Expression of Collagen-Binding α1β1 (VLA-1) and α2β1 (VLA-2) Integrins on CD4 and CD8 T Cells during Influenza Infection

Richter

Ray

Chapman

et al. 2007

The Journal of Immunology

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“…One possibility is that persistence of a peptide on the class II molecule provides an advantage for stable CD4 memory generation and maintenance. Although it is known that antigen persistence is not required to generate memory cells (42)(43)(44)(45), it is possible that continued opportunities to engage the CD4 T cells agonist ligand provides some advantage in the quantity or quality of memory T cells (29,(46)(47)(48)(49). Also, engagement of CD4 T cells, particularly follicular helper T cells, with antigen-specific B cells in the germinal center may be most efficient and long-lived for stable peptide:class II complexes (23).…”

Section: Discussionmentioning

confidence: 99%

Abortive activation of CD4 T cell responses during competitive priming in vivo

Weaver

Chaves

Sant

2009

Proc. Natl. Acad. Sci. U.S.A.

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Immunodominance refers to the highly selective peptide reactivity of T cells during an immune response. In this study, we tested the hypothesis that persistence of peptide:class II complexes is one key parameter that selects the final specificity of CD4 T cells. We found that low-stability peptide:class II complexes support the initial priming and expansion of CD4 T cells, but the expansion becomes strikingly aborted in the presence of competitive T cell responses to unrelated peptides. Our experiments revealed that for inhibition to occur, the competitive responses must be initiated by the same antigen presenting cell, and it is not because of competition for MHC binding. These studies not only provide an insight into the events that regulate competitive CD4 T cell priming in vivo, but also provide a previously undescribed conceptual framework to understand the parameters that select the final specificity of the T cell repertoire during pathogen or vaccine-induced immune responses.A ntigen presenting cells (APC) ingest antigens in peripheral tissues and, in response to inflammatory signals, migrate to lymph nodes (LNs), where they present peptide antigens bound to MHC class II molecules to recirculating CD4 T cells. The majority of T cells that are primed during an immune response are selectively skewed to one or a few of the many possible peptides from an antigen, resulting in a phenomenon known as immunodominance. Our laboratory has shown that an intrinsic biochemical property of the ligand recognized by the responding T cells, the kinetic stability of the peptide:MHC class II complexes, has the major role in both predicting and determining immunodominance (1). High-stability peptides elicit dominant responses, whereas low-stability peptides do not recruit detectable responses and are thus, ''cryptic'' (1). Selectivity in the repertoire of the presented peptide:class II complexes was shown to be modulated by DM editing in APC (2-4), and to be independent of the protein context in which those peptides resided (5).Recent findings describing the dynamic interactions of antigenbearing dendritic cells (DC) and T cells suggest that peptide off-rates from class II molecules may impact the immune response (6-8). The quality of signals received through the T cell antigen receptor (TcR) by peptides of different affinity for MHC class II has recently been suggested to regulate the fate and function of CD4 T cells (9, 10). Despite new methods that allow visualization of different phases of DC:T cell interactions to antigenic stimulus in vivo (11-18), the factors that contribute to efficient T cell activation and how the kinetic features of those interactions governs the fate of the responding T cells is still unknown. The decision for a T cell to ''stop'' and form long-lived contacts with a DC when scanning for cognate antigen may depend on multiple parameters, but antigen density (12) and peptide affinity for class II (19) have been shown to augment the frequency of prolonged DC:T cell contacts, increasing the efficienc...

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“…However, the relative contribution of direct cytopathic effects of viral replication or of an excessive or inappropriate immune reaction to the pathogenesis of IAV infection remains unclear (36,44,62). The pathogenic contribution of the T-cell response to IAV has been highlighted in studies using the mouse as a host (26,31,40). However, the rapidity with which IAVs, especially newly emerged highly pathogenic strains, induce pathology suggests that innate immunity is a main contributor (36,44,62).…”

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confidence: 99%

Suppression of Innate Immune Pathology by Regulatory T Cells during Influenza A Virus Infection of Immunodeficient Mice

Antunes¹,

Kassiotis²

2010

J Virol

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The viral infection of higher vertebrates elicits potent innate and adaptive host immunity. However, an excessive or inappropriate immune response also may lead to host pathology that often is more severe than the direct effects of viral replication. Therefore, several mechanisms exist that regulate the magnitude and class of the immune response. Here, we have examined the potential involvement of regulatory T (Treg) cells in limiting pathology induced by influenza A virus (IAV) infection. Using lymphocyte-deficient mice as hosts, we showed that Treg cell reconstitution resulted in a significant delay in weight loss and prolonged survival following infection. The adoptively transferred Treg cells did not affect the high rate of IAV replication in the lungs of lymphocyte-deficient hosts, and therefore their disease-ameliorating effect was mediated through the suppression of innate immune pathology. Mechanistically, Treg cells reduced the accumulation and altered the distribution of monocytes/macrophages in the lungs of IAV-infected hosts. This reduction in lung monocytosis was associated with a specific delay in monocyte chemotactic protein-2 (MCP-2) induction in the infected lungs. Nevertheless, Treg cells failed to prevent the eventual development of severe disease in lymphocyte-deficient hosts, which likely was caused by the ongoing IAV replication. Indeed, using T-cell-deficient mice, which mounted a T-cell-independent B cell response to IAV, we further showed that the combination of virusneutralizing antibodies and transferred Treg cells led to the complete prevention of clinical disease following IAV infection. Taken together, these results suggested that innate immune pathology and virus-induced pathology are the two main contributors to pathogenesis during IAV infection.

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Functional Specialization of Memory Th Cells Revealed by Expression of Integrin CD49b

Cited by 41 publications

References 46 publications

Collagen Distribution and Expression of Collagen-Binding α1β1 (VLA-1) and α2β1 (VLA-2) Integrins on CD4 and CD8 T Cells during Influenza Infection

Collagen Distribution and Expression of Collagen-Binding α1β1 (VLA-1) and α2β1 (VLA-2) Integrins on CD4 and CD8 T Cells during Influenza Infection

Abortive activation of CD4 T cell responses during competitive priming in vivo

Suppression of Innate Immune Pathology by Regulatory T Cells during Influenza A Virus Infection of Immunodeficient Mice

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