Requirement for CD4 T Cell Help in Generating Functional CD8 T Cell Memory

@article{Shedlock2003RequirementFC,
  title={Requirement for CD4 T Cell Help in Generating Functional CD8 T Cell Memory},
  author={Devon J. Shedlock and Hao Shen},
  journal={Science},
  year={2003},
  volume={300},
  pages={337 - 339}
}
Although primary CD8 responses to acute infections are independent of CD4 help, it is unknown whether a similar situation applies to secondary responses. We show that depletion of CD4 cells during the recall response has minimal effect, whereas depletion during the priming phase leads to reduced responses by memory CD8 cells to reinfection. Memory CD8 cells generated in CD4+/+ mice responded normally when transferred into CD4−/− hosts, whereas memory CD8 cells generated in CD4−/− mice mounted… 
Direct CD4 Help Provision following Interaction of Memory CD4 and CD8 T Cells with Distinct Antigen-Presenting Dendritic Cells
TLDR
It is reported that memory CD4 T cells can provide efficient help to memory CD8 T cells after interaction of the two lymphocytes with distinct dendritic cells, conditioned primarily not by Ag specificity but by activation status.
Memory CD4 T Cells Enhance Primary CD8 T-Cell Responses
TLDR
It is found that engaging endogenous memory Th1 cells at the time of CD8 T-cell priming results in increased CD8 effector responses to both bacterial and viral pathogens.
Mini‐review CD4 T cells are required for CD8 T cell memory generation
TLDR
The data invite us to drastically change the idea of CD4 help on CD8 responses because they show that the old dichotomy — Th‐dependent versus Th‐independentCD8 responses — is no longer accurate.
Cellswith Distinct Antigen-Presenting Dendritic Interaction of Memory CD4 and CD8 T Cells Direct CD4 Help Provision following
TLDR
It is reported that memory CD4 T cells can providecient help to memory CD8 T cells after interaction of the two lymphocytes with distinct dendritic cells, conditioned primarily not by Ag specificity but by activation status.
FoxP3+ regulatory CD4 T cells control the generation of functional CD8 memory
TLDR
It is reported that the Tregs act early, during the expansion phase of primary CD8 effectors, by fine tuning interleukin-2 exposure of CD8 memory precursors, which has implications for optimal vaccine development.
Phenotype and function of protective, CD4-independent CD8 T cell memory
TLDR
The potency of combined polyIC/CD40 to elicit CD8+ T cell memory in the absence of CD4 T cells suggests that it could be considered as a vaccine adjuvant in clinical situations where CD4 responses/numbers are compromised.
Helping Themselves: Optimal Virus-Specific CD4 T Cell Responses Require Help via CD4 T Cell Licensing of Dendritic Cells
TLDR
Activation of adoptively transferred Th cells during primary influenza A virus (IAV) infection enhances both the magnitude and functional breadth of endogenous primary IAV-specific CD4+ T cell responses.
Recall Responses by Helpless Memory CD8+ T Cells Are Restricted by the Up-Regulation of PD-11
TLDR
It is shown that CD4 help during priming is required for memory CD8+ T cell differentiation, and that stimulation of CD40 during primed rescues the helpless defects in the absence of CD4+ T cells.
The Development of Functional CD8 T Cell Memory after Listeria monocytogenes Infection Is Not Dependent on CD401
TLDR
It is shown that memory CD8 T cells generated in CD40-deficient mice show in vivo cytotoxicity and cytokine production equivalent to CD8 memory T cells from wild-type mice, indicating that CD40 ligation on CD9 T cells is not needed for the development of functional memoryCD8 T cell populations after Listeria infection.
CD4 T Cells Are Required for CD8 T Cell Survival during Both Primary and Memory Recall Responses1
TLDR
It is demonstrated that CD4 T cell help was not needed for the activation and effector differentiation of CD8 T cells during the primary response to vaccinia virus infection, but the activated CD8T cells showed poor survival, leading to a reduction in clonal expansion and a diminished, but stable CD8 memory pool.
...
...

References

SHOWING 1-10 OF 20 REFERENCES
A Role for CD40 Expression on CD8+ T Cells in the Generation of CD8+ T Cell Memory
TLDR
It is shown that generation of memory CD8+ T cells displaying an enhanced capacity for cell division and cytokine secretion required CD4 help but not CD40 expression by the APCs, suggesting that this interaction is fundamental for CD8- T cell memory generation.
CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes
TLDR
The results demonstrate that T-cell help is ‘programmed’ into CD8+ T cells during priming, conferring on these cells a hallmark of immune response memory: the capacity for functional expansion on re-encounter with antigen.
Role of CD4 T Cell Help and Costimulation in CD8 T Cell Responses During Listeria monocytogenes Infection 1
TLDR
Data show that in situations where infectious agents or immunogens can directly activate APC, CD8 T cell responses are less dependent on CD4 T cell help via the CD40-CD40L pathway but involve costimulation through CD137-CD137L and B7-CD28 interactions.
Diminished Primary and Secondary Influenza Virus-Specific CD8+ T-Cell Responses in CD4-Depleted Ig−/− Mice
TLDR
Both the magnitude and the localization profiles of virus-specific CD8+ T cells, though perhaps not their functional characteristics, are thus modified in mice lacking CD4- T cells.
Cutting Edge: CD4 and CD8 T Cells Are Intrinsically Different in Their Proliferative Responses1
TLDR
The results suggest that CD4 and CD8 T cells are programmed to undergo limited and extensive proliferation, respectively, to suit their function as regulator and effector cells.
CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection
TLDR
It is shown that CD4+ T cells are dispensable for short-term acute infection in which CD8+ CTL activity does not need to be sustained for more than 2 weeks, but under conditions of chronic infection, in which it takes several months or longer to clear the infection, CD4-cell function is critical.
CD4-deficient mice have reduced levels of memory cytotoxic T lymphocytes after immunization and show diminished resistance to subsequent virus challenge
TLDR
The potential importance of CD4+ T lymphocytes in generation of appropriate levels of CD(8+)-cell-mediated immunoprotective memory is underscored and has implications for vaccine efficacy in individuals with immune defects in which CD4 levels may be reduced, such as AIDS.
Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4
TLDR
In these mice, the development of CD8+ T cells and myeloid components is unaltered, indicating that expression of CD4 on progenitor cells and CD4+CD8+ (double positive) thymocytes is not obligatory, which is important to the understanding of immune disorders, including AIDS.
T-cell help for cytotoxic T lymphocytes is mediated by CD40–CD40L interactions
Although in vivo priming of CD8+ cytotoxic T lymphocytes (CTLs) generally requires the participation of CD4+ T-helper lymphocytes,, the nature of the ‘help’ provided to CTLs is unknown. One widely
Reduced Functional Capacity of CD8+ T Cells Expanded by Post-Exposure Vaccination of γ-Herpesvirus-Infected CD4-Deficient Mice1
TLDR
This experimental system provides an accessible model for evaluating postexposure vaccination protocols that might be used in diseases like HIV/AIDS, and the further need is to clarify the underlying molecular mechanisms and the relative significance of lack of CD4+ T help vs higher Ag load for these expanded CD8+ effector populations.
...
...