Novel phenotypes and migratory properties distinguish memory CD4 T cell subsets in lymphoid and lung tissue

Bingaman, Adam W.; Patke, Deepa S.; Mane, Vaishali R.; Ahmadzadeh, Mojgan; Ndejembi, Modesta; Bartlett, Stephen T.; Farber, Donna L.

doi:10.1002/eji.200526004

Cited by 81 publications

(124 citation statements)

References 34 publications

(49 reference statements)

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“…We then determined the subset composition of the T cells and used flow cytometry to first distinguish between CD4 þ and CD8 þ subsets, and then characterize the naive, memory and effector T cells using CD44 and CD25 expression as markers [27][28][29] (for a schematic see Figure 2a). Similar to our earlier observation in human CLL, 10 we found a decrease in the relative numbers of naive T cells, from 80 to 70% in the CD4 þ compartment, and a concomitant increase in the relative numbers of antigen-experienced memory T cells and from 15 to 25% in the blood of TCL1 transgenic mice with established CLL compared with non-transgenic littermates (Table 1; Figures 2b-e).…”

Section: Resultsmentioning

confidence: 99%

Development of CLL in the TCL1 transgenic mouse model is associated with severe skewing of the T-cell compartment homologous to human CLL

et al. 2011

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Chronic lymphocytic leukemia (CLL) cells require complex microenvironmental and immunologic interactions to survive and proliferate. Such interactions might be best recreated in animal models; however, this needs extensive verification. We therefore investigated the composition of the T-cell compartment in the El-TCL1 transgenic mouse, currently the most widely used murine model for CLL. Immunophenotyping and transplant approaches were used to define T-cell subsets at various stages of CLL. Analogous to human CLL, we observed a skewing of T-cell subsets from naive to antigen-experienced memory T cells that was more pronounced in lymph nodes than in blood. Transplantation of CLL into non-transgenic recipients was feasible without immunosuppression in a pure C57BL/6 background and resulted in the prominent skewing of the T cells of the recipient mice. Both in spontaneously developed CLL and in the transplantation setting, a loss in T-cell receptor diversity was observed, with a relevant number of clonal T-cell populations arising. This suggests that antigen-dependent differentiation toward the T memory pool is initiated by murine CLL cells. In summary, we validate the TCL1 transgenic mouse model for analysis of T-cell phenotypes and suggest a CLL-dependent antigen-driven skewing of T cells in these mice.

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Section: Resultsmentioning

confidence: 99%

Development of CLL in the TCL1 transgenic mouse model is associated with severe skewing of the T-cell compartment homologous to human CLL

et al. 2011

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“…Ag-specific and polyclonal CD4 ϩ CD62L high memory T cells express high levels of CD45RB (39), and although CD45RB expression by CD8 ϩ memory T cells has not been typically measured after viral infection (18), a population of CD8 ϩ CD45RB high CD62L high T cells thought to represent a T CM population is found in the liver after exposure to Plasmodium berghei (17,40). Although we detect CD8 ϩ tet ϩ CD62L high CD45RB low T cells in the lymphoid organs of chronically infected mice, treatment with antibiotics, a strategy used to experimentally induce memory immunity, led to the re-expression of CD45RB by TB10.4 20 -28 -specific CD8 ϩ T cells.…”

Section: Discussionmentioning

confidence: 99%

“…For example, identifying the CFP10 [32][33][34][35][36][37][38][39] epitope enabled us to show that CFP10-specific CD8 ϩ T cells, which accumulate in the lungs of mice following infection, have cytolytic activity in vivo (1). Elucidating the minimal epitopes presented by class I MHC allows accurate enumeration and characterization of Agspecific CD8 ϩ T cells primed during infection.…”

Section: Antigen-specific Cd8 ؉ T Cells and The Development Of Centramentioning

confidence: 99%

“…Thus, just as CFP10 [32][33][34][35][36][37][38][39] is an immunodominant epitope recognized by CD8 ϩ T cells in mice with the H-2 k haplotype (1), TB10.4 20 -28 is an immunodominant epitope in H-2 d BALB/c mice. TB10.4 20 -28 -specific CD8 ϩ T cells are found both in primary and secondary lymphoid organs, and accumulate in large numbers in the lung and in the bronchoalveolar compartment following aerosol infection with M. tuberculosis.…”

Section: Tb104 20 -28 Is An Immunodominant Ag Following Respiratory mentioning

confidence: 99%

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Antigen-Specific CD8+ T Cells and the Development of Central Memory during Mycobacterium tuberculosis Infection

Kamath

Woodworth

Behar

2006

The Journal of Immunology

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Whether true memory T cells develop in the face of chronic infection such as tuberculosis remains controversial. To address this question, we studied CD8+ T cells specific for the Mycobacterium tuberculosis ESAT6-related Ags TB10.3 and TB10.4. The shared epitope TB10.3/10.420–28 is presented by H-2 Kd, and 20–30% of the CD8+ T cells in the lungs of chronically infected mice are specific for this Ag following respiratory infection with M. tuberculosis. These TB10.3/10.420–28-specific CD8+ T cells produce IFN-γ and TNF and express CD107 on their cell surface, which indicates their likely role as CTL in vivo. Nearly all of the Ag-specific CD8+ T cells in the lungs of chronically infected mice had a T effector cell phenotype based on their low expression of CD62L and CD45RB. In contrast, a population of TB10.3/10.420–28-specific CD8+ T cells was identified in the lymphoid organs that express high levels of CD62L and CD45RB. Antibiotic treatment to resolve the infection led to a contraction of the Ag-specific CD8+ T cell population and was accompanied by an increase in the proportion of CD8+ T cells with a central memory phenotype. Finally, challenge of memory-immune mice with M. tuberculosis was accompanied by significant expansion of TB10.3/10.420–28-specific CD8+ T cells, which suggests that these cells are in fact functional memory T cells.

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“…The transfer of 1°effectors to unprimed mice can protect against lethal challenge (8)(9)(10), and studies demonstrating memory CD4 + T-cell protection in mice deficient for CD8 + T and B cells suggest that an important helper-independent protective contribution of memory CD4 + T cells may be mediated directly by the 2°e ffectors (11)(12)(13). In addition, IAV-specific 1°effector (7,10) and memory (14,15) CD4 + T cells isolated from the lung and from secondary lymphoid organs (SLO) display distinct functional and phenotypic characteristics. Whether 2°effectors comprise a similarly heterogeneous population is unknown.…”

Section: Cytokines | Viral Infection | Immune Regulationmentioning

confidence: 99%

Memory CD4⁺T-cell–mediated protection depends on secondary effectors that are distinct from and superior to primary effectors

Strutt

McKinstry

Kuang

et al. 2012

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

112

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Whether differences between naive cell-derived primary (1°) and memory cell-derived secondary (2°) CD4+ T-cell effectors contribute to protective recall responses is unclear. Here, we compare these effectors directly after influenza A virus infection. Both develop with similar kinetics, but 2° effectors accumulate in greater number in the infected lung and are the critical component of memory CD4+ T-cell–mediated protection against influenza A virus, independent of earlier-acting memory-cell helper functions. Phenotypic, functional, and transcriptome analyses indicate that 2° effectors share organ-specific expression patterns with 1° effectors but are more multifunctional, with more multicytokine (IFN-γ+/IL-2+/TNF+)-producing cells and contain follicular helper T-cell populations not only in the spleen and draining lymph nodes but also in the lung. In addition, they express more CD127 and NKG2A but less ICOS and Lag-3 than 1° effectors and express higher levels of several genes associated with survival and migration. Targeting two differentially expressed molecules, NKG2A and Lag-3, reveals differential regulation of 1° and 2° effector functions during pathogen challenge.

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Novel phenotypes and migratory properties distinguish memory CD4 T cell subsets in lymphoid and lung tissue

Cited by 81 publications

References 34 publications

Development of CLL in the TCL1 transgenic mouse model is associated with severe skewing of the T-cell compartment homologous to human CLL

Development of CLL in the TCL1 transgenic mouse model is associated with severe skewing of the T-cell compartment homologous to human CLL

Antigen-Specific CD8+ T Cells and the Development of Central Memory during Mycobacterium tuberculosis Infection

Memory CD4⁺T-cell–mediated protection depends on secondary effectors that are distinct from and superior to primary effectors

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Novel phenotypes and migratory properties distinguish memory CD4 T cell subsets in lymphoid and lung tissue

Cited by 81 publications

References 34 publications

Development of CLL in the TCL1 transgenic mouse model is associated with severe skewing of the T-cell compartment homologous to human CLL

Development of CLL in the TCL1 transgenic mouse model is associated with severe skewing of the T-cell compartment homologous to human CLL

Antigen-Specific CD8+ T Cells and the Development of Central Memory during Mycobacterium tuberculosis Infection

Memory CD4+T-cell–mediated protection depends on secondary effectors that are distinct from and superior to primary effectors

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Memory CD4⁺T-cell–mediated protection depends on secondary effectors that are distinct from and superior to primary effectors