Antigen-Experienced CD4 T Cells Display a Reduced Capacity for Clonal Expansion In Vivo That Is Imposed by Factors Present in the Immune Host

Merica, Rebecca; Khoruts, Alexander; Pape, Kathryn A.; Reinhardt, R. Lee; Jenkins, Marc K.

doi:10.4049/jimmunol.164.9.4551

Cited by 60 publications

(58 citation statements)

References 36 publications

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“…The residual Ag-specific T cell population is long lasting, but is defective in the ability to proliferate and secrete cytokines upon secondary challenge (85,86). This anergic state of Ag-experienced T cells was shown to require Ag persistence in the immune host environment (86,87) In our study the secondary administration of HEL was able to induce T cell response at the same magnitude observed in the primary HEL response. This nonanergic state of the secondary T cell response may result from the existence of HEL on B cells in the absence of exogenous HEL, thus preserving the naive environment of the recipients.…”

Section: Cd8␣supporting

confidence: 60%

Marginal Zone, but Not Follicular B Cells, Are Potent Activators of Naive CD4 T Cells

Attanavanich

Kearney

2004

The Journal of Immunology

235

210

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The early involvement of marginal zone (MZ) B lymphocytes in T-independent immune responses is well established. In this study we compared the abilities of MZ and follicular (FO) B cells to collaborate with T cells. After immunization with soluble hen egg lysozyme, both MZ and FO B cells captured Ag and migrated to T cell areas in the response to hen egg lysozyme. MZ B cells were far superior to FO B cells in inducing CD4+ T cell expansion both in vitro and in vivo. MZ, but not FO, B cells, after interaction with T cells, differentiated into plasma cells, and in addition they stimulated Ag-specific CD4+ T cells to produce high levels of Th1-like cytokines upon primary stimulation in vitro. These results indicate that MZ B cells rapidly and effectively capture soluble Ag and activate CD4+ T cells to become effector T cells. The enhanced capacity of MZ B cells to prime T cells in this study appeared to be intrinsic to MZ B cells, as both MZ and FO B cell populations express an identical Ag receptor.

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Section: Cd8␣supporting

confidence: 60%

Marginal Zone, but Not Follicular B Cells, Are Potent Activators of Naive CD4 T Cells

Attanavanich

Kearney

2004

The Journal of Immunology

235

210

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“…In contrast to this result, Mercia et al (25) found that TCR Tg memory cells proliferated more after transfer to naïve hosts. Our results may differ for several reasons: first, they transferred a large number of TCR Tg cells rather than studying an endogenous CD4 T cell response as we have done.…”

Section: Discussionmentioning

confidence: 44%

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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“…The ability of IgG to potentiate Ag presentation has been demonstrated in vitro (31)(32)(33)(34)(35) and ex vivo (34,35), and has been implied in vivo (30,36,37). Here, we are able to directly visualize in vivo that IgG2a-mediated feedback enhancement of Ab responses to OVA is preceded by a rapid expansion of specific CD4 ϩ T cells.…”

Section: Discussionmentioning

confidence: 58%

IgG2a-Mediated Enhancement of Antibody and T Cell Responses and Its Relation to Inhibitory and Activating Fcγ Receptors

Getahun

Dahlström

Wernersson

et al. 2004

The Journal of Immunology

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A number of studies in experimental animal models point to an important role of FcγRs in autoimmunity and allergy. In this study, we investigate how the production of IgG, an early step in the chain of events leading to inflammation, is regulated by activating and inhibitory FcγRs. IgG Abs are known to feedback-enhance Ab responses to soluble Ags, and this effect requires activating FcγRs. To test proliferation of Th cells, mice were adoptively transferred with CD4+ T cells expressing a transgenic OVA-specific TCR before immunization with IgG2a anti-2,4,6-trinitrophenyl (TNP) plus OVA-TNP or with OVA-TNP alone. IgG2a induced a significant increase in OVA-specific T cell numbers, which preceded the OVA-specific Ab response and was dependent on the FcRγ chain. The role of the inhibitory FcγRIIB in Ab responses was studied in mice lacking this receptor. Although IgG2a enhanced primary Ab responses, development of germinal centers, and immunological memory in wild-type mice, enhancement was markedly stronger in FcγRIIB−/− mice. The presented data are compatible with the hypothesis that the mechanism behind IgG2a-mediated up-regulation of Ab responses involves increased Ag presentation to CD4+ T cells by FcγR+ APCs. Our observations also illustrate the intricate immunoregulatory role of IgG Abs. On the one hand, they enhance Ab responses via activating FcγRs, and on the other hand, they set an upper limit for the same Ab response via FcγRIIB.

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Antigen-Experienced CD4 T Cells Display a Reduced Capacity for Clonal Expansion In Vivo That Is Imposed by Factors Present in the Immune Host

Cited by 60 publications

References 36 publications

Marginal Zone, but Not Follicular B Cells, Are Potent Activators of Naive CD4 T Cells

Marginal Zone, but Not Follicular B Cells, Are Potent Activators of Naive CD4 T Cells

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

IgG2a-Mediated Enhancement of Antibody and T Cell Responses and Its Relation to Inhibitory and Activating Fcγ Receptors

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