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Development and Function of Protective and Pathologic Memory CD4 T Cells.

Jaigirdar SA, MacLeod MK - Front Immunol (2015)

Bottom Line: As key orchestrators and mediators of immunity, CD4 T cells are central to the vast majority of adaptive immune responses.Generated following an immune response, memory CD4 T cells retain pertinent information about their activation environment enabling them to make rapid effector responses upon reactivation.A greater understanding of these factors has the potential to aid the design of more effective vaccines and to improve regulation of pathologic CD4 T cells, such as in the context of autoimmunity and allergy.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, University of Glasgow , Glasgow , UK.

ABSTRACT
Immunological memory is one of the defining features of the adaptive immune system. As key orchestrators and mediators of immunity, CD4 T cells are central to the vast majority of adaptive immune responses. Generated following an immune response, memory CD4 T cells retain pertinent information about their activation environment enabling them to make rapid effector responses upon reactivation. These responses can either benefit the host by hastening the control of pathogens or cause damaging immunopathology. Here, we will discuss the diversity of the memory CD4 T cell pool, the signals that influence the transition of activated T cells into that pool, and highlight how activation requirements differ between naïve and memory CD4 T cells. A greater understanding of these factors has the potential to aid the design of more effective vaccines and to improve regulation of pathologic CD4 T cells, such as in the context of autoimmunity and allergy.

No MeSH data available.


Related in: MedlinePlus

Intrinsic changes in memory CD4 T cells which enhance their response to activation. There are a number of factors that can contribute to the distinct responses of memory CD4 T cells as compared to their naïve counterparts. T cell receptor (TCR) triggering can be enhanced in two ways: in polyclonal populations, the cells with the highest affinity for the antigen can come to dominate the response (1) alternatively, or in addition, the CD3 TCR-signaling complex is clustered more effectively in memory than naïve CD4 T cells (2). Intracellular signaling molecules are also altered: memory CD4 T cells contain more Zap 70 than naïve T cells (3) and TCR activation leads to increased phosphorylation of the MAPK, p38 (4). Changes in cell surface proteins, such as chemokine receptors (5) and integrins (6), affect cell migration and location enabling memory CD4 T cells to migrate rapidly to inflamed sites or reside permanently in pathogen-targeted tissues. Changes in gene transcription before and following T cell reactivation are also evident. Epigenetic differences between naïve and memory CD4 T cells enable more rapid transcription of effector molecules, such as cytokines, thereby accelerating the control and clearance of pathogens (17, 97–101).
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Figure 2: Intrinsic changes in memory CD4 T cells which enhance their response to activation. There are a number of factors that can contribute to the distinct responses of memory CD4 T cells as compared to their naïve counterparts. T cell receptor (TCR) triggering can be enhanced in two ways: in polyclonal populations, the cells with the highest affinity for the antigen can come to dominate the response (1) alternatively, or in addition, the CD3 TCR-signaling complex is clustered more effectively in memory than naïve CD4 T cells (2). Intracellular signaling molecules are also altered: memory CD4 T cells contain more Zap 70 than naïve T cells (3) and TCR activation leads to increased phosphorylation of the MAPK, p38 (4). Changes in cell surface proteins, such as chemokine receptors (5) and integrins (6), affect cell migration and location enabling memory CD4 T cells to migrate rapidly to inflamed sites or reside permanently in pathogen-targeted tissues. Changes in gene transcription before and following T cell reactivation are also evident. Epigenetic differences between naïve and memory CD4 T cells enable more rapid transcription of effector molecules, such as cytokines, thereby accelerating the control and clearance of pathogens (17, 97–101).

Mentions: A major tenet of vaccination is that memory T cells are better equipped to control and clear a pathogen compared to their naïve counterparts. “Better” encompasses a range of functions including speed, sensitivity, and the type of response the memory cell can deliver (Figure 2).


Development and Function of Protective and Pathologic Memory CD4 T Cells.

Jaigirdar SA, MacLeod MK - Front Immunol (2015)

Intrinsic changes in memory CD4 T cells which enhance their response to activation. There are a number of factors that can contribute to the distinct responses of memory CD4 T cells as compared to their naïve counterparts. T cell receptor (TCR) triggering can be enhanced in two ways: in polyclonal populations, the cells with the highest affinity for the antigen can come to dominate the response (1) alternatively, or in addition, the CD3 TCR-signaling complex is clustered more effectively in memory than naïve CD4 T cells (2). Intracellular signaling molecules are also altered: memory CD4 T cells contain more Zap 70 than naïve T cells (3) and TCR activation leads to increased phosphorylation of the MAPK, p38 (4). Changes in cell surface proteins, such as chemokine receptors (5) and integrins (6), affect cell migration and location enabling memory CD4 T cells to migrate rapidly to inflamed sites or reside permanently in pathogen-targeted tissues. Changes in gene transcription before and following T cell reactivation are also evident. Epigenetic differences between naïve and memory CD4 T cells enable more rapid transcription of effector molecules, such as cytokines, thereby accelerating the control and clearance of pathogens (17, 97–101).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561815&req=5

Figure 2: Intrinsic changes in memory CD4 T cells which enhance their response to activation. There are a number of factors that can contribute to the distinct responses of memory CD4 T cells as compared to their naïve counterparts. T cell receptor (TCR) triggering can be enhanced in two ways: in polyclonal populations, the cells with the highest affinity for the antigen can come to dominate the response (1) alternatively, or in addition, the CD3 TCR-signaling complex is clustered more effectively in memory than naïve CD4 T cells (2). Intracellular signaling molecules are also altered: memory CD4 T cells contain more Zap 70 than naïve T cells (3) and TCR activation leads to increased phosphorylation of the MAPK, p38 (4). Changes in cell surface proteins, such as chemokine receptors (5) and integrins (6), affect cell migration and location enabling memory CD4 T cells to migrate rapidly to inflamed sites or reside permanently in pathogen-targeted tissues. Changes in gene transcription before and following T cell reactivation are also evident. Epigenetic differences between naïve and memory CD4 T cells enable more rapid transcription of effector molecules, such as cytokines, thereby accelerating the control and clearance of pathogens (17, 97–101).
Mentions: A major tenet of vaccination is that memory T cells are better equipped to control and clear a pathogen compared to their naïve counterparts. “Better” encompasses a range of functions including speed, sensitivity, and the type of response the memory cell can deliver (Figure 2).

Bottom Line: As key orchestrators and mediators of immunity, CD4 T cells are central to the vast majority of adaptive immune responses.Generated following an immune response, memory CD4 T cells retain pertinent information about their activation environment enabling them to make rapid effector responses upon reactivation.A greater understanding of these factors has the potential to aid the design of more effective vaccines and to improve regulation of pathologic CD4 T cells, such as in the context of autoimmunity and allergy.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, University of Glasgow , Glasgow , UK.

ABSTRACT
Immunological memory is one of the defining features of the adaptive immune system. As key orchestrators and mediators of immunity, CD4 T cells are central to the vast majority of adaptive immune responses. Generated following an immune response, memory CD4 T cells retain pertinent information about their activation environment enabling them to make rapid effector responses upon reactivation. These responses can either benefit the host by hastening the control of pathogens or cause damaging immunopathology. Here, we will discuss the diversity of the memory CD4 T cell pool, the signals that influence the transition of activated T cells into that pool, and highlight how activation requirements differ between naïve and memory CD4 T cells. A greater understanding of these factors has the potential to aid the design of more effective vaccines and to improve regulation of pathologic CD4 T cells, such as in the context of autoimmunity and allergy.

No MeSH data available.


Related in: MedlinePlus