Differentiation of memory B and T cells

Kalia, Vandana; Sarkar, Surojit; Gourley, Tania; Rouse, Barry T.; Ahmed, Rafi

doi:10.1016/j.coi.2006.03.020

Cited by 150 publications

(138 citation statements)

References 89 publications

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“…In contrast, a low concentration of IL-2 mostly promoted the development of memory-like cells with reduced in vitro cytotoxic effects (39). Consequently, effector differentiation is not a prerequisite for generation of memory CTL (40). Remarkably, in our study, we found that most of HIV-specific CD8 ϩ T cells that proliferated were expressing lytic machinery (granzyme B), and therefore, they may have had cytotoxic activity.…”

Section: Discussionmentioning

confidence: 45%

Phenotypic and Functional Analysis of Immune CD8+ T Cell Responses Induced by a Single Injection of a HIV DNA Vaccine in Mice

Arrode

Hegde

Mani

et al. 2007

The Journal of Immunology

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HIV DNA vaccines are potent inducers of cell-mediated immune (CMI) response in mice but elicit poor HIV-specific IFN-γ-producing T cells in monkeys and humans. In this study, we performed kinetic analyses on splenocytes of BALB/c mice that were immunized by a single injection with a unique DNA vaccine. Using IFN-γ-ELISPOT and multiparametric FACS analysis, we characterized the induced CMI response. We found that the response was detectable for at least 63 wk. ELISPOT detection of IFN-γ-producing T cells showed a profile with two waves separated by a long period of minimal response. Multiparametric FACS analysis showed two populations of CD3+CD8+ T cells that were specific for all HIV Ags. These cells had similar robust proliferation abilities and contained granzyme B. However, only a few produced IFN-γ. Both IFN-γ-producing and non-IFN-γ-producing HIV-specific CD8+ T cells were detected in the early stage (week (W)1 and W2 postimmunization (PI)), in the prolonged intermediate period of minimal response (W4-W26 PI), and in the final late phase of increased response (W30-W63 PI). Our longitudinal characterization showed that both subsets of cells underwent expansion, contraction, and memory generation/maintenance phases throughout the lifespan of the animal. Altogether, these findings bring insight to the heterogeneity of the immune T cell response induced by a single immunization with this DNA and strengthen the concept that used of the IFN-γ-ELISPOT assay alone may be insufficient to detect critical T cell responses to candidate HIV vaccines.

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Section: Discussionmentioning

confidence: 45%

Phenotypic and Functional Analysis of Immune CD8+ T Cell Responses Induced by a Single Injection of a HIV DNA Vaccine in Mice

Arrode

Hegde

Mani

et al. 2007

The Journal of Immunology

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“…Terminally differentiated effector T (Temra) cells and effector memory T (Tem) cells circulate mainly in the peripheral tissue where they recognize antigens, mount a rapid cytokine response and deliver cytotoxic molecules to destroy antigen‐positive cells 8. In contrast, naive and central memory T (Tcm) cells preferentially migrate through the secondary lymphoid tissues where they are primed by mature dendritic cells, expand and differentiate into effector and effector memory cells that will recirculate to the peripheral tissue 9, 10. Recent studies have demonstrated that antigen presentation and naive T cell priming can also occur outside secondary lymphoid organs, within tumours in ectopic lymphoid‐like structures, named tertiary lymphoid structures,11 as an expedited mechanism for priming tumour‐reactive T cells.…”

Section: Introductionmentioning

confidence: 99%

Polyfunctional response by ImmTAC (IMCgp100) redirected CD8⁺ and CD4⁺ T cells

et al. 2017

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SummaryThe success of immune system‐based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilizing monoclonal T cell receptors (TCRs) against cancer (ImmTAC™ molecules: fusion proteins consisting of a soluble, affinity enhanced TCR and an anti‐CD3 scFv antibody) were previously shown to redirect CD8+ and CD4+ T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognizing a peptide derived from the melanoma‐specific protein, gp100, presented by HLA‐A*0201) efficiently redirects and activates effector and memory cells from both CD8+ and CD4+ repertoires. Using isolated subpopulations of T cells, we find that both terminally differentiated and effector memory CD8+ T cells redirected by IMCgp100 are potent killers of melanoma cells. Furthermore, CD4+ effector memory T cells elicit potent cytotoxic activity leading to melanoma cell killing upon redirection by IMCgp100. The majority of T cell subsets belonging to both the CD8+ and CD4+ repertoires secrete key pro‐inflammatory cytokines (tumour necrosis factor‐α, interferon‐γ, interleukin‐6) and chemokines (macrophage inflammatory protein‐1α‐β, interferon‐γ‐inducible protein‐10, monocyte chemoattractant protein‐1). At an individual cell level, IMCgp100‐redirected T cells display a polyfunctional phenotype, which is a hallmark of a potent anti‐cancer response. This study demonstrates that IMCgp100 induces broad immune responses that extend beyond the induction of CD8+ T cell‐mediated cytotoxicity. These findings are of particular importance because IMCgp100 is currently undergoing clinical trials as a single agent or in combination with check point inhibitors for patients with malignant melanoma.

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“…interferon gamma ͉ interleukin 2 ͉ proliferation ͉ LCMV ͉ recall I mmunological memory is a defining characteristic of the adaptive immune response and can be manifested by antigenspecific B cells and CD4 and CD8 T cells (1). Work of the last 10 years has tremendously advanced our knowledge of CD8 T cell memory (2).…”

mentioning

confidence: 99%

CD4 memory T cells divide poorly in response to antigen because of their cytokine profile

MacLeod

McKee

Crawford

et al. 2008

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

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Immunological memory is a hallmark of adaptive immunity, and understanding T cell memory will be central to the development of effective cell-mediated vaccines. The characteristics and functions of CD4 memory cells have not been well defined. Here we demonstrate that the increased size of the secondary response is solely a consequence of the increased antigen-specific precursor frequency within the memory pool. Memory cells proliferated less than primary responding cells, even within the same host. By analyzing the entry of primary and memory cells into the cell cycle, we found that the two populations proliferated similarly until day 5; after this time, fewer of the reactivated memory cells proliferated. At this time, fewer of the reactivated memory cells made IL-2 than primary responding cells, but more made IFN␥. Both these factors affected the low proliferation of the memory cells, because either exogenous IL-2 or inhibition of IFN␥ increased the proliferation of the memory cells.interferon gamma ͉ interleukin 2 ͉ proliferation ͉ LCMV ͉ recall

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Differentiation of memory B and T cells

Cited by 150 publications

References 89 publications

Phenotypic and Functional Analysis of Immune CD8+ T Cell Responses Induced by a Single Injection of a HIV DNA Vaccine in Mice

Phenotypic and Functional Analysis of Immune CD8+ T Cell Responses Induced by a Single Injection of a HIV DNA Vaccine in Mice

Polyfunctional response by ImmTAC (IMCgp100) redirected CD8⁺ and CD4⁺ T cells

CD4 memory T cells divide poorly in response to antigen because of their cytokine profile

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Differentiation of memory B and T cells

Cited by 150 publications

References 89 publications

Phenotypic and Functional Analysis of Immune CD8+ T Cell Responses Induced by a Single Injection of a HIV DNA Vaccine in Mice

Phenotypic and Functional Analysis of Immune CD8+ T Cell Responses Induced by a Single Injection of a HIV DNA Vaccine in Mice

Polyfunctional response by ImmTAC (IMCgp100) redirected CD8+ and CD4+ T cells

CD4 memory T cells divide poorly in response to antigen because of their cytokine profile

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Polyfunctional response by ImmTAC (IMCgp100) redirected CD8⁺ and CD4⁺ T cells