Cutting Edge: Perforin Down-Regulates CD4 and CD8 T Cell-Mediated Immune Responses to a Transplanted Organ

AbstractNeutrophils are innate immune cells involved in the elimination of pathogens and can also induce adaptive immune responses. Nα and Nβ neutrophils have been described with distinct in vitro capacity to generate antigen-specific CD8 T-cell responses. However, how these cell types exert their role in vivo and how manipulation of Nβ/Nα ratio influences vaccine-mediated immune responses are not known. In this study, we find that these neutrophil subtypes show distinct migratory and motility patterns and different ability to interact with CD8 T cells in the spleen following vaccinia virus (VACV) infection. Moreover, after analysis of adhesion, inflammatory, and migration markers, we observe that Nβ neutrophils overexpress the α4β1 integrin compared to Nα. Finally, by inhibiting α4β1 integrin, we increase the Nβ/Nα ratio and enhance CD8 T-cell responses to HIV VACV-delivered antigens. These findings provide significant advancements in the comprehension of neutrophil-based control of adaptive immune system and their relevance in vaccine design.

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Direct and Indirect endocrine-mediated suppression of human endometrial CD8+T cell cytotoxicity

Scientific Reports ◽

10.1038/s41598-021-81380-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Z. Shen ◽

M. Rodriguez-Garcia ◽

M. V. Patel ◽

C. R. Wira

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Cytotoxic Activity ◽

Cd8 T Cells ◽

Immune Cells ◽

Cd8 T Cell ◽

Gynecological Cancers ◽

Protective Strategies ◽

T Cell Cytotoxicity

AbstractRegulation of endometrial (EM) CD8+T cells is essential for successful reproduction and protection against pathogens. Suppression of CD8+T cells is necessary for a tolerogenic environment that promotes implantation and pregnancy. However, the mechanisms regulating this process remain unclear. Sex hormones are known to control immune responses directly on immune cells and indirectly through the tissue environment. When the actions of estradiol (E2), progesterone (P) and TGFβ on EM CD8+T cells were evaluated, cytotoxic activity, perforin and granzymes were directly suppressed by E2 and TGFβ but not P. Moreover, incubation of polarized EM epithelial cells with P, but not E2, increased TGFβ secretion. These findings suggest that E2 acts directly on CD8+T cell to suppress cytotoxic activity while P acts indirectly through induction of TGFβ production. Understanding the mechanisms involved in regulating endometrial CD8+T cells is essential for optimizing reproductive success and developing protective strategies against genital infections and gynecological cancers.

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Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses

Journal of Experimental Medicine ◽

10.1084/jem.20170161 ◽

2017 ◽

Vol 214 (9) ◽

pp. 2563-2572 ◽

Cited By ~ 9

Author(s):

Spencer W. Stonier ◽

Andrew S. Herbert ◽

Ana I. Kuehne ◽

Ariel Sobarzo ◽

Polina Habibulin ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

Ebola Virus ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Cd8 T Cell ◽

Marburg Virus ◽

Antibody Responses ◽

Cd4 T Cell ◽

Cell Responses

Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4+ T cell responses but limited CD8+ T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity.

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